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Zhang X, Li Y, Gong Y, Jia N, Luo Y, Cao J, Yuan Y, Wang Z, Zhi X. 1,25(OH) 2D 3 protected against LPS-induced acute lung injury through modulation of gut microbiota. J Nutr Biochem 2025:109970. [PMID: 40403854 DOI: 10.1016/j.jnutbio.2025.109970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 05/10/2025] [Accepted: 05/19/2025] [Indexed: 05/24/2025]
Abstract
This study investigated whether gut and lung microbiota mediated the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] against acute lung injury (ALI). We evaluated the impact of various 1,25(OH)2D3 doses on lipopolysaccharide (LPS)-induced ALI and characterized microbial changes in both intestinal and pulmonary communities. Correlation between lung and gut microbiota was assessed. To further explore the role of intestinal flora, a depletion model was established using antibiotics (ABX). Our results indicated that 1,25(OH)2D3 alleviated LPS-induced ALI, as evidenced by reduced pathological damage, downregulated expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), increased levels of anti-inflammatory cytokine (IL-10), and suppressed TLR4/NF-κB and JNK pathways. LPS reduced α diversity and altered β diversity and composition of intestinal microbes, which were partially reversed by 1,25(OH)2D3 intervention. Notably, 1,25(OH)2D3 enhanced gut microbiota diversity and elevated the relative abundance of Muribaculaceae and Lachnospiraceae genus. Importantly, depletion of gut flora with ABX eliminated the anti-inflammatory effects of 1,25(OH)2D3, including its inhibition of LPS-induced cytokine expressions and pathway activation. Although LPS did not significantly affect the diversity of lung microbiota, it seemed to change its composition and induced a significant correlation between intestinal and pulmonary microbial communities, which was attenuated by 1,25(OH)₂D₃. In conclusion, our findings suggested that the protective effects of 1,25(OH)2D3 against LPS-induced ALI might be partially mediated by gut microbiota, highlighting a potential mechanism for vitamin D's immunomodulatory activity in inflammatory lung disease.
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Affiliation(s)
- Xiaoming Zhang
- Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China
| | - Ye Li
- Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China
| | - Yiting Gong
- Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China
| | - Ning Jia
- Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China
| | - Yuanqing Luo
- Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China
| | - Jianrong Cao
- Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China
| | - Yan Yuan
- Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China
| | - Zitian Wang
- Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China
| | - Xueyuan Zhi
- Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China.
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Luo WJ, Dong XW, Ye H, Zhao QS, Zhang QB, Guo WY, Liu HW, Xu F. Vitamin D 1,25-Dihydroxyvitamin D 3 reduces lipid accumulation in hepatocytes by inhibiting M1 macrophage polarization. World J Gastrointest Oncol 2024; 16:4685-4699. [PMID: 39678811 PMCID: PMC11577380 DOI: 10.4251/wjgo.v16.i12.4685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 09/09/2024] [Accepted: 10/08/2024] [Indexed: 11/12/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD), which is a significant liver condition associated with metabolic syndrome, is the leading cause of liver diseases globally and its prevalence is on the rise in most nations. The protective impact of vitamin D on NAFLD and its specific mechanism remains unclear. AIM To examine the role of vitamin D in NAFLD and how vitamin D affects the polarization of hepatic macrophages in NAFLD through the vitamin D receptor (VDR)-peroxisome proliferator activated receptor (PPAR)γ pathway. METHODS Wild-type C57BL/6 mice were provided with a high-fat diet to trigger NAFLD model and administered 1,25-dihydroxy-vitamin D [1,25(OH)2D3] supplementation. 1,25(OH)2D3 was given to RAW264.7 macrophages that had been treated with lipid, and a co-culture with AML12 hepatocytes was set up. Lipid accumulation, lipid metabolism enzymes, M1/M2 phenotype markers, proinflammatory cytokines and VDR-PPARγ pathway were determined. RESULTS Supplementation with 1,25(OH)2D3 relieved hepatic steatosis and decreased the proinflammatory M1 polarization of hepatic macrophages in NAFLD. Administration of 1,25(OH)2D3 suppressed the proinflammatory M1 polarization of macrophages induced by fatty acids, thereby directly relieving lipid accumulation and metabolism in hepatocytes. The VDR-PPARγ pathway had a notable impact on reversing lipid-induced proinflammatory M1 polarization of macrophages regulated by the administration of 1,25(OH)2D3. CONCLUSION Supplementation with 1,25(OH)2D3 improved hepatic steatosis and lipid metabolism in NAFLD, linked to its capacity to reverse the proinflammatory M1 polarization of hepatic macrophages, partially by regulating the VDR-PPARγ pathway. The involvement of 1,25(OH)2D3 in inhibiting fatty-acid-induced proinflammatory M1 polarization of macrophages played a direct role in relieving lipid accumulation and metabolism in hepatocytes.
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Affiliation(s)
- Wen-Jing Luo
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Xian-Wen Dong
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Hua Ye
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Qiao-Su Zhao
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Qiu-Bo Zhang
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Wen-Ying Guo
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Hui-Wei Liu
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Feng Xu
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
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Ullah A, Chen Y, Singla RK, Cao D, Shen B. Exploring cytokines dynamics: Uncovering therapeutic concepts for metabolic disorders in postmenopausal women- diabetes, metabolic bone diseases, and non-alcohol fatty liver disease. Ageing Res Rev 2024; 101:102505. [PMID: 39307315 DOI: 10.1016/j.arr.2024.102505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/18/2024] [Accepted: 09/12/2024] [Indexed: 09/26/2024]
Abstract
Menopause is an age-related change that persists for around one-third of a woman's life. Menopause increases the risk of metabolic illnesses such as diabetes, osteoporosis (OP), and nonalcoholic fatty liver disease (NAFLD). Immune mediators (pro-inflammatory cytokines), such as interleukin-1 (IL-1), IL-6, IL-17, transforming growth factor (TGF), and tumor necrosis factor (TNF), exacerbate the challenges of a woman undergoing menopause by causing inflammation and contributing to the development of these metabolic diseases in postmenopausal women. Furthermore, studies have shown that anti-inflammatory cytokines such as interleukin-1 receptor antagonists (IL-1Ra), IL-2, and IL-10 have a double-edged effect on diabetes and OP. Likewise, several interferon (IFN) members are double-edged swords in the OP. Therefore, addressing these immune mediators precisely may be an approach to improving the health of postmenopausal women. Hence, considering the significant changes in these cytokines, the present review focuses on the latest findings concerning the molecular mechanisms by which pro- and anti-inflammatory cytokines (interleukins) impact postmenopausal women with diabetes, OP, and NAFLD. Furthermore, we comprehensively discuss the therapeutic approaches that identify cytokines as therapeutic targets, such as hormonal therapy, physical activities, natural inhibitors (drugs), and others. Finally, this review aims to provide valuable insights into the role of cytokines in postmenopausal women's diabetes, OP, and NAFLD. Deeply investigating the mechanisms and therapeutic interventions involved will address the characteristics of immune mediators (cytokines) and improve the management of these illnesses, thereby enhancing the general quality of life and health of the corresponding populations of women.
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Affiliation(s)
- Amin Ullah
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yongxiu Chen
- Gynecology Department, Guangdong Women and Children Hospital, No. 521, Xingnan Road, Panyu District, Guangzhou 511442, China
| | - Rajeev K Singla
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India
| | - Dan Cao
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Bairong Shen
- Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
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Wang Y, Jiao L, Qiang C, Chen C, Shen Z, Ding F, Lv L, Zhu T, Lu Y, Cui X. The role of matrix metalloproteinase 9 in fibrosis diseases and its molecular mechanisms. Biomed Pharmacother 2024; 171:116116. [PMID: 38181715 DOI: 10.1016/j.biopha.2023.116116] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/25/2023] [Accepted: 12/29/2023] [Indexed: 01/07/2024] Open
Abstract
Fibrosis is a process of tissue repair that results in the slow creation of scar tissue to replace healthy tissue and can affect any tissue or organ. Its primary feature is the massive deposition of extracellular matrix (mainly collagen), eventually leading to tissue dysfunction and organ failure. The progression of fibrotic diseases has put a significant strain on global health and the economy, and as a result, there is an urgent need to find some new therapies. Previous studies have identified that inflammation, oxidative stress, some cytokines, and remodeling play a crucial role in fibrotic diseases and are essential avenues for treating fibrotic diseases. Among them, matrix metalloproteinases (MMPs) are considered the main targets for the treatment of fibrotic diseases since they are the primary driver involved in ECM degradation, and tissue inhibitors of metalloproteinases (TIMPs) are natural endogenous inhibitors of MMPs. Through previous studies, we found that MMP-9 is an essential target for treating fibrotic diseases. However, it is worth noting that MMP-9 plays a bidirectional regulatory role in different fibrotic diseases or different stages of the same fibrotic disease. Previously identified MMP-9 inhibitors, such as pirfenidone and nintedanib, suffer from some rather pronounced side effects, and therefore, there is an urgent need to investigate new drugs. In this review, we explore the mechanism of action and signaling pathways of MMP-9 in different tissues and organs, hoping to provide some ideas for developing safer and more effective biologics.
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Affiliation(s)
- Yuling Wang
- Department of Cardiovascular Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Linke Jiao
- Department of Cardiovascular Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Caoxia Qiang
- Department of Traditional Chinese Medicine, Tumor Hospital Affiliated to Nantong University, Jiangsu, China
| | - Chen Chen
- Department of Cardiovascular Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zihuan Shen
- Department of Cardiovascular Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Fan Ding
- Department of Cardiovascular Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Lifei Lv
- Department of Cardiovascular Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Tingting Zhu
- Department of Cardiovascular Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yingdong Lu
- Department of Cardiovascular Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiangning Cui
- Department of Cardiovascular Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
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Shi L, Zhou L, Han M, Zhang Y, Zhang Y, Yuan XX, Lu HP, Wang Y, Yang XL, Liu C, Wang J, Liang P, Liu SA, Liu XJ, Cheng J, Lin SM. Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF β1/Smad3 and NF-κB signaling pathways. World J Gastroenterol 2023; 29:2798-2817. [PMID: 37274069 PMCID: PMC10237113 DOI: 10.3748/wjg.v29.i18.2798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 03/08/2023] [Accepted: 04/10/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Hepatic fibrosis is a serious condition, and the development of hepatic fibrosis can lead to a series of complications. However, the pathogenesis of hepatic fibrosis remains unclear, and effective therapy options are still lacking. Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1 (NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis, but its role in diseases including hepatic fibrosis remains undefined. Therefore, additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.
AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.
METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups, comprising the normal, fibrosis, and calcitriol treatment groups, and liver fibrosis was modeled by carbon tetrachloride (CCl4). To evaluate the level of hepatic fibrosis in every group, serological and pathological examinations of the liver were conducted. TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells. NS3TP1, α-smooth muscle actin (α-SMA), collagen I, and collagen III in every group were examined using a Western blot and real-time quantitative polymerase chain reaction. The activity of the transforming growth factor beta 1 (TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected. The statistical analysis of the data was performed using the Student’s t test.
RESULTS NS3TP1 promoted the activation, proliferation, and differentiation of hepatic stellate cells (HSCs) and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways, as evidenced by the presence of α-SMA, collagen I, collagen III, p-smad3, and p-p65 in LX-2 cells, which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference. The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression, as shown by the luciferase assay. NS3TP1 inhibited the apoptosis of HSCs. Moreover, both Smad3 and p65 could bind to NS3TP1, and p65 increased the promoter activity of NS3TP1, while NS3TP1 increased the promoter activity of TGFβ1 receptor I, as indicated by coimmunoprecipitation and luciferase assay results. Both in vivo and in vitro, treatment with calcitriol dramatically reduced the expression of NS3TP1. Calcitriol therapy-controlled HSCs activation, proliferation, and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice. Furthermore, calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.
CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique, prospective therapeutic target in hepatic fibrosis.
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Affiliation(s)
- Liu Shi
- Department of Infectious Disease Medicine, The First Hospital Affiliated to Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Li Zhou
- China-Japan Friendship Hospital, Department of Infectious Disease China-Japan Friendship Hospital, Beijing 100029, China
| | - Ming Han
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yu Zhang
- The Division of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yang Zhang
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xiao-Xue Yuan
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Hong-Ping Lu
- Institute of Liver Diseases, Beijing Pan-Asia Tongze Institute of Biomedicine Co., Ltd, Beijing 100015, China
| | - Yun Wang
- The Division of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xue-Liang Yang
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Chen Liu
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Jun Wang
- Beijing Key Laboratory of Emerging Infectious Diseases, Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Pu Liang
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Shun-Ai Liu
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xiao-Jing Liu
- Department of Infectious Disease Medicine, The First Hospital Affiliated to Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Jun Cheng
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Shu-Mei Lin
- Department of Infectious Disease Medicine, The First Hospital Affiliated to Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
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Zhao M, Ma L, Honda T, Kato A, Ohshiro T, Yokoyama S, Yamamoto K, Ito T, Imai N, Ishizu Y, Nakamura M, Kawashima H, Tsuji NM, Ishigami M, Fujishiro M. Astaxanthin Attenuates Nonalcoholic Steatohepatitis with Downregulation of Osteoprotegerin in Ovariectomized Mice Fed Choline-Deficient High-Fat Diet. Dig Dis Sci 2023; 68:155-163. [PMID: 35397697 DOI: 10.1007/s10620-022-07489-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 03/14/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Postmenopausal estrogen decline increases the risk of developing nonalcoholic steatohepatitis (NASH), and it might accelerate progression to cirrhosis and hepatocellular carcinoma. AIMS This study aimed to investigate a novel therapy for postmenopausal women who are diagnosed with NASH. METHODS Seven-week-old female C57BL/6 J mice were divided into three experimental groups as follows: (1) sham operation (SHAM group), (2) ovariectomy (OVX group), and (3) ovariectomy + 0.02% astaxanthin (OVX + ASTX group). These three groups of mice were fed a choline-deficient high-fat (CDHF) diet for 8 weeks. Blood serum and liver tissues were collected to examine liver injury, histological changes, and hepatic genes associated with NASH. An in vitro study was performed with the hepatic stellate cell line LX-2. RESULTS The administration of ASTX significantly improved pathological NASH with suppressed steatosis, inflammation, and fibrosis, in comparison with those in the OVX-induced estrogen deficiency group. As a result, liver injury was also attenuated with reduced levels of alanine aminotransferase and aspartate transaminase. In addition, our study found that ASTX supplementation decreased hepatic osteoprotegerin (OPG) in vivo, a possible factor that contributes to NASH development. In vitro, this study further confirmed that ASTX has an inhibitory effect on the secretion of OPG in LX-2 human hepatic stellate cells. CONCLUSIONS Our findings suggest that ASTX alleviates CDHF-OVX-induced pathohistological NASH with downregulated OPG, possibly via suppression of the transforming growth factor beta pathway. ASTX could has promise for use in postmenopausal women diagnosed with NASH.
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Affiliation(s)
- Meng Zhao
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Lingyun Ma
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Asuka Kato
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
- ITOCHU Collaborative Research-Molecular Targeted Cancer Treatment for Next Generation, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Taichi Ohshiro
- ITOCHU Collaborative Research-Molecular Targeted Cancer Treatment for Next Generation, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Shinya Yokoyama
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Norihiro Imai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Noriko M Tsuji
- Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
- Division of Immune Homeostasis, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
- Department of Food Science, Jumonji University, Saitama, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan
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Pierce JL, Perrien DS. Do Interactions of Vitamin D 3 and BMP Signaling Hold Implications in the Pathogenesis of Fibrodysplasia Ossificans Progressiva? Curr Osteoporos Rep 2021; 19:358-367. [PMID: 33851285 PMCID: PMC8515998 DOI: 10.1007/s11914-021-00673-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/16/2021] [Indexed: 11/24/2022]
Abstract
PURPOSE OF REVIEW Fibrodysplasia ossificans progressiva (FOP) is a debilitating rare disease known for episodic endochondral heterotopic ossification (HO) caused by gain-of-function mutations in ACVR1/ALK2. However, disease severity varies among patients with identical mutations suggesting disease-modifying factors, including diet, may have therapeutic implications. The roles of vitamin D3 in calcium metabolism and chondrogenesis are known, but its effects on BMP signaling and chondrogenesis are less studied. This review attempts to assess the possibility of vitamin D's effects in FOP by exploring relevant intersections of VD3 with mechanisms of FOP flares. RECENT FINDINGS In vitro and in vivo studies suggest vitamin D suppresses inflammation, while clinical studies suggest that vitamin D3 protects against arteriosclerosis and inversely correlates with non-genetic intramuscular HO. However, the enhancement of chondrogenesis, BMP signaling, and possibly Activin A expression by vitamin D may be more relevant in FOP. There appears to be little potential for vitamin D to reduce HO in FOP, but testing the potential for excess vitamin D to promote HO may be warranted.
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Affiliation(s)
- Jessica L Pierce
- Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, WMRB 1027, Atlanta, GA, 30232, USA
| | - Daniel S Perrien
- Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, WMRB 1027, Atlanta, GA, 30232, USA.
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Chen T, Zuo X, Wang S, Yu P, Yuan J, Wei S, Chen J, Sun Y, Gao Y, Li X. The effect of vitamin D supplementation on the progression of fibrosis in patients with chronic liver disease: A protocol for a systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e20296. [PMID: 32384521 PMCID: PMC7220037 DOI: 10.1097/md.0000000000020296] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 04/16/2020] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Hepatic fibrosis (HF) is the common pathological basis of chronic liver disease (CLD). Many data indicate that serum vitamin D (VD) levels in patients with liver fibrosis are significantly lower than those without liver fibrosis, and lower level of serum 1,25(OH)2D3 is also an independent risk factor for patients with liver fibrosis combined with other diseases. VD has the functions of anti-fibrosis, regulating cell proliferation and differentiation, anti-inflammatory, and immune regulation, Therefore, serum 1,25(OH)2D3 level may be negatively correlated with the progression of liver fibrosis. But there is absent convincing evidence-based medicine to confirm the efficacy of VD supplementation for CLD. Thus, we aimed to conduct this meta-analysis to summarize the efficacy of VD supplementation on the progression of fibrosis in patients with CLD. METHODS The study only selects clinical randomized controlled trials of VD supplementation for CLD. We will search each database from the built-in until September 2020. The English literature mainly searches Cochrane Library, Pubmed, EMBASE, and Web of Science. While the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Meanwhile, we will retrieve clinical trial registries and gray literature. Two researchers worked independently on literature selection, data extraction and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on the heterogeneity. The serum VD level, hepatic function and serological indexes of hepatic fibrosis were evaluated as the main outcomes. While several secondary outcomes were also evaluated in this study. The statistical analysis of this Meta-analysis was conducted by RevMan software version 5.3. RESULTS This meta-analysis will further determine the beneficial efficacy of VD supplementation on the progression of fibrosis in patients with CLD. CONCLUSION This study determines the positive efficacy of VD supplementation for CLD. ETHICS AND DISSEMINATION This review is based solely on a secondary study of published literatures and does not require ethics committee approval. Its conclusion will be disseminated in conference papers, magazines or peer-reviewed journals. REGISTRATION NUMBER INPLASY202040054.
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Affiliation(s)
- Tiantian Chen
- Department of Rheumatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072
| | - Xiaohong Zuo
- School of basic medical sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137
| | - Shengju Wang
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072
| | - Penglong Yu
- Department of Rheumatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072
| | - Jie Yuan
- School of basic medical sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137
| | - Shujun Wei
- School of basic medical sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137
| | - Jiayi Chen
- Department of Rheumatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072
| | - Yue Sun
- School of basic medical sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137
| | - Yongxiang Gao
- College of International Education of Chengdu University of Traditional Chinese Medicine, PR China
| | - Xueping Li
- School of basic medical sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137
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