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Ezaddoustdar A, Kalina D, Bielohuby M, Boehm M, Wygrecka M. dEREGulated pathways: unraveling the role of epiregulin in skin, kidney, and lung fibrosis. Am J Physiol Cell Physiol 2025; 328:C617-C626. [PMID: 39750963 DOI: 10.1152/ajpcell.00813.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 12/24/2024] [Accepted: 12/24/2024] [Indexed: 01/04/2025]
Abstract
The epidermal growth factor receptor (EGFR) signaling pathway is an evolutionary conserved mechanism to control cell behavior during tissue development and homeostasis. Deregulation of this pathway has been associated with abnormal cell behavior, including hyperproliferation, senescence, and an inflammatory cell phenotype, thereby contributing to pathologies across a variety of organs, including the kidneys, skin, and lungs. To date, there are seven distinct EGFR ligands described. Although binding of these ligands to the receptor is cell type-specific and spatio-temporally controlled with distinct affinities and kinetics, epiregulin (EREG) stands out as a long-acting EGFR ligand that emerges under pathological conditions, particularly in tissue fibrosis. Although EREG has been extensively studied in cancer, its contribution to the maladaptive remodeling of tissue is elusive. The aim of this review is to highlight the role of EREG in skin, kidney, and lung fibrosis and to discuss opportunities for therapeutic intervention.
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Affiliation(s)
- Aysan Ezaddoustdar
- Center for Infection and Genomics of the Lung, Faculty of Medicine, Justus Liebig University, Member of the German Center for Lung Research, Giessen, Germany
| | | | | | | | - Malgorzata Wygrecka
- Center for Infection and Genomics of the Lung, Faculty of Medicine, Justus Liebig University, Member of the German Center for Lung Research, Giessen, Germany
- CSL Innovation GmbH, Marburg, Germany
- Institute for Lung Health, Justus Liebig University, Giessen, Germany
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Wang J, Li J, Zhou L, Hou H, Zhang K. Regulation of epidermal barrier function and pathogenesis of psoriasis by serine protease inhibitors. Front Immunol 2024; 15:1498067. [PMID: 39737188 PMCID: PMC11683130 DOI: 10.3389/fimmu.2024.1498067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 11/27/2024] [Indexed: 01/01/2025] Open
Abstract
Serine protease inhibitors (Serpins) are a protein superfamily of protease inhibitors that are thought to play a role in the regulation of inflammation, immunity, tumorigenesis, coagulation, blood pressure and cancer metastasis. Serpins is enriched in the skin and play a vital role in modulating the epidermal barrier and maintaining skin homeostasis. Psoriasis is a chronic inflammatory immune-mediated skin disease. At present, most serpins focus on the pathogenesis of psoriasis vulgaris. Only a small number, such as the mutation of SerpinA1/A3/B3, are involved in the pathogenesis of GPP. SerpinA12 and SerpinG1 are significantly elevated in the serum of patients with psoriatic arthritis, but their specific mechanism of action in psoriatic arthritis has not been reported. Some Serpins, including SerpinA12, SerpinB2/B3/B7, play multiple roles in skin barrier function and pathogenesis of psoriasis. The decrease in the expression of SerpinA12, SerpinB7 deficiency and increase in expression of SerpinB3/4 in the skin can promote inflammation and poor differentiation of keratinocyte, with damaged skin barrier. Pso p27, derived from SerpinB3/B4, is an autoantigen that can enhance immune response in psoriasis. SerpinB2 plays a role in maintaining epidermal barrier integrity and inhibiting keratinocyte proliferation. Here we briefly introduce the structure, functional characteristics, expression and distribution of serpins in skin and focus on the regulation of serpins in the epidermal barrier function and the pathogenic role of serpins in psoriasis.
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Affiliation(s)
- Juanjuan Wang
- Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China
- State Key Breeding Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China
| | - Junqin Li
- Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China
- State Key Breeding Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China
| | - Ling Zhou
- Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China
- State Key Breeding Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China
| | - Hui Hou
- Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China
- State Key Breeding Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China
| | - Kaiming Zhang
- Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China
- State Key Breeding Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, China
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Chen Y, Chen L, Huang S, Yang L, Wang L, Yang F, Huang J, Ding X. Predicting novel biomarkers for early diagnosis and dynamic severity monitoring of human ulcerative colitis. Front Genet 2024; 15:1429482. [PMID: 39144720 PMCID: PMC11321978 DOI: 10.3389/fgene.2024.1429482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 07/18/2024] [Indexed: 08/16/2024] Open
Abstract
Background Ulcerative colitis is an emerging global health concern that poses a significant threat to human health and can progress to colorectal cancer if not diagnosed and treated promptly. Currently, the biomarkers used clinically for diagnosis and dynamic severity monitoring lack disease specificity. Methods Mouse models induced with 2%, 2.5%, and 3% DSS were utilized to simulate human UC with varying severities of inflammation. Transcriptome sequencing technology was employed to identify differentially expressed genes (DEGs) between the control group and each treatment group. Functional enrichment analysis of the KEGG database was performed for shared DEGs among the three treatment groups. DEGs that were significantly and strongly correlated with DSS concentrations were identified using Spearman correlation analysis. Human homologous genes of the interested DEGs were searched in the HomoloGene database, and their regulation patterns in UC patients were validated using the GSE224758 dataset. These genes were then submitted to the DisGeNET database to identify their known associations with human diseases. Online tools, including SignalP 6.0 and DeepTMHMM 1.0, were used to predict signal peptides and transmembrane helices in the amino acid sequences of human genes homologous to the DEGs of interest. Results A total of 1,230, 995, and 2,214 DEGs were identified in the 2%, 2.5%, and 3% DSS-induced groups, respectively, with 668 DEGs common across all three groups. These shared DEGs were primarily associated with signaling transport, pathogenesis, and immune response. Through extensive screening, LGI2 and PRSS22 were identified as potentially novel biomarkers with higher specificity and ease of detection for the early diagnosis and dynamic severity monitoring of human UC, respectively. Conclusion We have identified two potentially novel biomarkers, LGI2 and PRSS22, which are easy of detection and more specific for human UC. These findings provide new insights into the accurate diagnosis and dynamic monitoring of this persistent disease.
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Affiliation(s)
- Yu Chen
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Li Chen
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Sheng Huang
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Li Yang
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Li Wang
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Feiyun Yang
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Jinxiu Huang
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Xiuliang Ding
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
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Wei HF, Zhang RF, Zhao YC, Tong XS. SERPINB7 as a prognostic biomarker in cervical cancer: Association with immune infiltration and facilitation of the malignant phenotype. Heliyon 2023; 9:e20184. [PMID: 37809412 PMCID: PMC10559959 DOI: 10.1016/j.heliyon.2023.e20184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 09/06/2023] [Accepted: 09/13/2023] [Indexed: 10/10/2023] Open
Abstract
Purpose The purpose of this study was to investigate the expression patterns, predictive significance, and roles in the immune microenvironment of Serpin Family-B Member 7 (SERPINB7) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Methods The expression of SERPINB7 and its prognostic relevance were evaluated using RNA-seq data from The Cancer Genome Atlas. SERPINB7 regulation of CESC cell growth and metastasis was investigated using MTT, scratch, and Transwell assays. In vivo effects of SERPINB7 were examined in xenograft model mice and differentially expressed genes (DEGs) associated with SERPINB7 were identified to explore its functional role in oncogenesis. Associations between SERPINB7 levels, chemosensitivity, and immune infiltration were assessed, and mutations and methylation of SERPINB7 were evaluated using the cBioPortal and MethSurv databases, respectively. Results SERPINB7 was up-regulated in CESC samples as well as in other tumors, and patients with higher SERPINB7A mRNA levels exhibited shorter overall survival. The area under the curve for the use of SERPINB7 in CESC diagnosis was above 0.9, and the gene was shown to regulate tumor cell proliferation and metastasis in vitro and in vivo. Overall, 398 DEGs enriched in key CESC progression-related signaling pathways were identified. SERPINB7 expression was additionally correlated with intratumoral immune infiltration and immune checkpoint activity. Patients expressing higher SERPINB7 levels exhibited distinct chemosensitivity profiles, and methylation of the SERPINB7 gene was linked to CESC patient prognostic outcomes. Conclusion SERPINB7 was found to be a crucial regulator of CESC progression, prognosis, and the tumor immune microenvironment, highlighting its potential as a diagnostic and prognostic biomarker and target for CESC immunotherapy.
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Affiliation(s)
- Hua-Fang Wei
- Department of Internal Medicine-1, Jilin Cancer Hospital, Changchun, Jilin, People's Republic of China
| | - Rui-Feng Zhang
- Department of Internal Medicine-1, Jilin Cancer Hospital, Changchun, Jilin, People's Republic of China
- Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Yue-Chen Zhao
- Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Xian-Shuang Tong
- Department of Internal Medicine-1, Jilin Cancer Hospital, Changchun, Jilin, People's Republic of China
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WFDC12-overexpressing contributes to the development of atopic dermatitis via accelerating ALOX12/15 metabolism and PAF accumulation. Cell Death Dis 2023; 14:185. [PMID: 36882395 PMCID: PMC9992393 DOI: 10.1038/s41419-023-05686-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 03/09/2023]
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczema-like skin lesions, dry skin, severe itching, and recurrent recurrence. The whey acidic protein four-disulfide core domain gene WFDC12 is highly expressed in skin tissue and up-regulated in the skin lesions of AD patients, but its role and relevant mechanism in AD pathogenesis have not been studied yet. In this study, we found that the expression of WFDC12 was closely related to clinical symptoms of AD and the severity of AD-like lesions induced by DNFB in transgenic mice. WFDC12-overexpressing in the epidermis might promote the migration of skin-presenting cells to lymph nodes and increase Th cell infiltration. Meanwhile, the number and ratio of immune cells and mRNA levels of cytokines were significantly upregulated in transgenic mice. In addition, we found that ALOX12/15 gene expression was upregulated in the arachidonic acid metabolism pathway, and the corresponding metabolite accumulation was increased. The activity of epidermal serine hydrolase decreased and the accumulation of platelet-activating factor (PAF) increased in the epidermis of transgenic mice. Collectively, our data demonstrate that WFDC12 may contribute to the exacerbation of AD-like symptoms in DNFB-induced mouse model by enhancing arachidonic acid metabolism and PAF accumulation and that WFDC12 may be a potential therapeutic target for human atopic dermatitis.
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Zhao F, Zhang C, Li G, Zheng H, Gu L, Zhou H, Xiao Y, Wang Z, Yu J, Hu Y, Zeng F, Wang X, Zhao Q, Hu J, Yue C, Zhou P, Huang N, Hao Y, Wu W, Cui K, Li W, Li J. A role for whey acidic protein four-disulfide-core 12 (WFDC12) in the pathogenesis and development of psoriasis disease. Front Immunol 2022; 13:873720. [PMID: 36148224 PMCID: PMC9485559 DOI: 10.3389/fimmu.2022.873720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
Whey acidic protein four-disulfide core domain protein 12 (WFDC12) has been implicated in the pathogenesis of psoriasis but the specific molecular mechanism is not clearly defined. In this study, we found the expression of WFDC12 protein closely correlated with psoriasis. WFDC12 in keratinocyte might increase infiltration of Langerhans cells (LCs) and monocyte-derived dendritic cells (moDDCs), up-regulating the co-stimulation molecular CD40/CD86. Th1 cells in lymph nodes were higher in K14-WFDC12 transgenic psoiasis-like mice. Meanwhile, the mRNA of IL-12 and IFN-γ in the lesion skin was significantly increased in transgenic mice. Moreover, we found that the expression of the proteins that participated in the retinoic acid–related pathway and immune signaling pathway was more changed in the lesion skin of K14-WFDC12 transgenic psoriasis-like mice. Collectively, the results implied that WFDC12 might affect the activation of the retinoic acid signaling pathway and regulate the infiltration of DC cells in the skin lesions and lymph nodes, thereby inducing Th1 cells differentiation and increasing the secretion of IFN-γ to exacerbate psoriasis in mice.
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Affiliation(s)
- Fulei Zhao
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Chen Zhang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Guolin Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Huaping Zheng
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Linna Gu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Hong Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Yuanyuan Xiao
- Department of Obstetrics and Gynecology, West China Second Hospital of Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Zhen Wang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Jiadong Yu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Yawen Hu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Fanlian Zeng
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Xiaoyan Wang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Qixiang Zhao
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Jing Hu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Chengcheng Yue
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Pei Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Nongyu Huang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Yan Hao
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Wenling Wu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Kaijun Cui
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
| | - Wei Li
- Department of Dermatology, Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jiong Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
- *Correspondence: Jiong Li,
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SerpinB7 deficiency contributes to development of psoriasis via calcium-mediated keratinocyte differentiation dysfunction. Cell Death Dis 2022; 13:635. [PMID: 35864103 PMCID: PMC9304369 DOI: 10.1038/s41419-022-05045-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 06/17/2022] [Accepted: 06/27/2022] [Indexed: 01/21/2023]
Abstract
Defective execution of proteases and protease inhibitors that mediate abnormal signaling cascades is emerging as a key contributor to skin diseases, such as psoriasis. SerpinB7 is identified as a skin-specific endogenous protease inhibitor, but the role and underlying mechanism in psoriasis are poorly understood. Here we found that SerpinB7 is highly expressed in psoriatic keratinocytes of patients and imiquimod-induced psoriatic lesions in mice. SerpinB7-/- mice showed abnormal epidermal barrier integrity and skin architecture in homeostasis, and aggravated psoriatic lesion with inhibiting terminal differentiation and increasing inflammatory cells infiltration compared to SerpinB7+/+ mice after Imiquimod treatment. Mechanistically, SerpinB7 deficiency results in excessive proliferation and impaired differentiation, as well as increased chemokines and antimicrobial peptide expression in normal human epidermal keratinocyte and mouse primary keratinocyte. Transcriptomics and proteomics results showed that the SeprinB7 deficiency affected keratinocyte differentiation and proinflammatory cytokines, possibly by affecting the calcium ion channel-related proteins. Notably, we demonstrated that SerpinB7 deficiency prevented the increase in intracellular Ca2+ influx, which was partly eliminated by the intracellular Ca2+ chelator BAPTA-AM. Our findings first described the critical role of SerpinB7 in the regulation of keratinocyte differentiation and psoriatic microenvironment mediated via keratinocytes' intracellular calcium flux, proposing a new candidate for therapeutic targets in psoriasis.
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Mohd Noor AA, Azlan M, Mohd Redzwan N. Orchestrated Cytokines Mediated by Biologics in Psoriasis and Its Mechanisms of Action. Biomedicines 2022; 10:biomedicines10020498. [PMID: 35203707 PMCID: PMC8962336 DOI: 10.3390/biomedicines10020498] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 02/12/2022] [Accepted: 02/14/2022] [Indexed: 12/27/2022] Open
Abstract
Psoriasis is an autoimmune disease mediated by disturbed T cells and other immune cells, and is defined by deep-red, well-demarcated skin lesions. Due to its varied etiologies and indefinite standard pathogenesis, it is challenging to consider the right treatment exclusively for each psoriasis patient; thus, researchers yearn to seek even more precise treatments other than topical treatment and systemic therapy. Using biologics to target specific immune components, such as upregulated cytokines secreted by activated immune cells, is the most advanced therapy for psoriasis to date. By inhibiting the appropriate pro-inflammatory cytokines, cellular signaling can be altered and, thus, can inhibit further downstream inflammatory pathways. Herein, the roles of cytokines with their mechanisms of action in progressing psoriasis and how the usage of biologics alleviates cellular inflammation are discussed. In addition, other potential pro-inflammatory cytokines, with their mechanism of action, are presented herein. The authors hope that this gathered information may benefit future research in expanding the discovery of targeted psoriasis therapy.
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Affiliation(s)
- Aina Akmal Mohd Noor
- Immunology Department, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia;
| | - Maryam Azlan
- School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia;
| | - Norhanani Mohd Redzwan
- Immunology Department, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia;
- Correspondence: ; Tel.: +60-9767-6130
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Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis. Genes (Basel) 2020; 11:genes11101155. [PMID: 33007857 PMCID: PMC7600703 DOI: 10.3390/genes11101155] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 09/28/2020] [Accepted: 09/29/2020] [Indexed: 02/08/2023] Open
Abstract
Psoriasis is an immune-mediated inflammatory skin disease with a complex etiology involving environmental and genetic factors. A better insight into related genomic alteration helps design precise therapies leading to better treatment outcome. Gene expression in psoriasis can provide relevant information about the altered expression of mRNA transcripts, thus giving new insights into the disease onset. Techniques for transcriptome analyses, such as microarray and RNA sequencing (RNA-seq), are relevant tools for the discovery of new biomarkers as well as new therapeutic targets. This review summarizes the findings related to the contribution of keratinocytes in the pathogenesis of psoriasis by an in-depth review of studies that have examined psoriatic transcriptomes in the past years. It also provides valuable information on reconstructed 3D psoriatic skin models using cells isolated from psoriatic patients for transcriptomic studies.
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