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Tamura Y, Takata K, Eguchi A, Maeda M, Kataoka Y. Age-related changes in NG2-expressing telocytes of rat stomach. PLoS One 2021; 16:e0249729. [PMID: 33822814 PMCID: PMC8023479 DOI: 10.1371/journal.pone.0249729] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 03/23/2021] [Indexed: 11/18/2022] Open
Abstract
NG2 immunoreactive cells (NG2 cells) are found in the brain and peripheral tissues including the skin, intestinal tracts, and bladder. In a previous study, we observed the presence of NG2 cells in the stomach using bioluminescence imaging techniques in NG2-firefly luciferase (fLuc) transgenic (Tg) rats. Here, we aimed to identify and characterize NG2 cells in the adult rat stomach. Immunohistochemical studies showed that NG2 cells were mainly present in the lamina propria and most of the cells were gastric telocytes, co-expressing CD34, and platelet-derived growth factor receptor alpha (PDGFRα), with a small oval-shaped cell body and extremely long and thin cellular prolongations. In the rat stomach, NG2-expressing telocytes comprised two subpopulations: NG2+/CD34+/PDGFRα+ and NG2+/CD34+/PDGFRα-. Furthermore, we showed that the expression of NG2 gene in the aged rat stomach decreased relative to that of the young rat stomach and the decline of NG2 expression in aged rats was mainly observed in NG2+/CD34+/PDGFRα+ telocytes. These findings suggested age-related alterations in NG2+/CD34+/PDGFRα+ telocytes of rat stomach.
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Affiliation(s)
- Yasuhisa Tamura
- Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Chuo-ku, Kobe, Japan
- Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Chuo-ku, Kobe, Japan
| | - Kumi Takata
- Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Chuo-ku, Kobe, Japan
- Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Chuo-ku, Kobe, Japan
| | - Asami Eguchi
- Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Chuo-ku, Kobe, Japan
- Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Chuo-ku, Kobe, Japan
| | - Mitsuyo Maeda
- Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Chuo-ku, Kobe, Japan
- Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Chuo-ku, Kobe, Japan
| | - Yosky Kataoka
- Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Chuo-ku, Kobe, Japan
- Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Chuo-ku, Kobe, Japan
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Suzuki T, Eng DG, McClelland AD, Pippin JW, Shankland SJ. Cells of NG2 lineage increase in glomeruli of mice following podocyte depletion. Am J Physiol Renal Physiol 2018; 315:F1449-F1464. [PMID: 30019931 PMCID: PMC6293287 DOI: 10.1152/ajprenal.00118.2018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Under certain circumstances, podocytes can be partially replaced following their loss in disease. The inability of podocytes to proliferate suggests that replacement derives from other cell types. Because neural/glial antigen 2 (NG2)-expressing cells can serve as progenitors in other organs and because herein we showed increased NG2 staining in podocytes following their loss in experimental focal segmental glomerulosclerosis, we used lineage tracing in NG2-CreER tdTomato mice to test the hypothesis that partial podocyte replacement might derive from this cell population. The percentage of glomeruli with red fluorescence protein (RFP)-labeled NG2 cells increased following podocyte depletion, which was augmented by enalapril. However, BrdU was not detected in RFP-labeled cells, consistent with the migration of these cells to the glomerulus. Within glomeruli, RFP-labeled cells did not coexpress podocyte proteins (p57, synaptopodin, nephrin, or podocin) but did coexpress markers for mesangial (α8 integrin, PDGFβ receptor) and parietal epithelial cells (PAX8, src-suppressed C-kinase substrate). These results suggest that following podocyte depletion, cells of NG2 lineage do not serve as adult podocyte progenitors but have the ability to transdifferentiate to mesangial and parietal epithelial cell fates.
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Affiliation(s)
- Taihei Suzuki
- Division of Nephrology, University of Washington School of Medicine , Seattle, Washington
| | - Diana G Eng
- Division of Nephrology, University of Washington School of Medicine , Seattle, Washington
| | - Aaron D McClelland
- Division of Nephrology, University of Washington School of Medicine , Seattle, Washington
| | - Jeffrey W Pippin
- Division of Nephrology, University of Washington School of Medicine , Seattle, Washington
| | - Stuart J Shankland
- Division of Nephrology, University of Washington School of Medicine , Seattle, Washington
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Tamura Y, Takata K, Eguchi A, Kataoka Y. In vivo monitoring of hair cycle stages via bioluminescence imaging of hair follicle NG2 cells. Sci Rep 2018; 8:393. [PMID: 29321681 PMCID: PMC5762894 DOI: 10.1038/s41598-017-18763-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 12/15/2017] [Indexed: 12/17/2022] Open
Abstract
Hair growth occurs periodically in a cycle that consists of three different phases: growth, regression, and resting. The length of each phase is regulated by both intrinsic and extrinsic factors throughout life, and influenced by physiological and pathological conditions. Elongation of the resting phase and shortening of the growth phase occur during physiological ageing and in baldness, respectively. In vivo discrimination of each phase of the hair cycle can be used to research for regeneration of hair follicles as well as to evaluate the efficacy of hair regrowth treatments in the same individual. Here we show that NG2+ epithelial cells in the hair follicles encompass bulge stem cells, and that the number of hair follicle NG2 cells underwent dramatic changes during the hair cycle. Transgenic rats with expression of firefly luciferase gene in NG2 cells were generated to monitor the hair cycle in vivo. Hair follicle NG2 cells were clearly visualized via bioluminescence imaging to study each phase of the hair cycle in the rats, from infancy to old age.
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Affiliation(s)
- Yasuhisa Tamura
- Cellular Function Imaging Team, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan. .,Multi-Modal Microstructure Analysis Unit, RIKEN CLST-JEOL Collaboration Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
| | - Kumi Takata
- Cellular Function Imaging Team, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan
| | - Asami Eguchi
- Cellular Function Imaging Team, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.,Multi-Modal Microstructure Analysis Unit, RIKEN CLST-JEOL Collaboration Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan
| | - Yosky Kataoka
- Cellular Function Imaging Team, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.,Multi-Modal Microstructure Analysis Unit, RIKEN CLST-JEOL Collaboration Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan
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Lu LL, Sun J, Lai JJ, Jiang Y, Bai LH, Zhang LD. Neuron-glial antigen 2 overexpression in hepatocellular carcinoma predicts poor prognosis. World J Gastroenterol 2015; 21:6649-6659. [PMID: 26074703 PMCID: PMC4458775 DOI: 10.3748/wjg.v21.i21.6649] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Revised: 12/30/2014] [Accepted: 01/16/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether neuron-glial antigen 2 (NG2) could be an effective prognostic marker in hepatocellular carcinoma (HCC).
METHODS: NG2 expression was semi-quantitatively scored from the immunohistochemistry (IHC) data based on the number of positive cells and the staining intensity. A total of 132 HCC specimens and 96 adjacent noncancerous tissue samples were analyzed by IHC for NG2 protein expression. To confirm the NG2 expression levels observed by IHC, we measured NG2 expression in 30 randomly selected tumor and adjacent noncancerous tissue samples by quantitative real-time polymerase chain reaction and Western blot. The correlations between NG2 protein expression and the clinicopathological features of HCC patients were analyzed using the χ2 test. To assess the prognostic value of NG2 for HCC, the association between NG2 expression and survival was analyzed using the Kaplan-Meier method with the log-rank test. To further evaluate the prognostic value of NG2 expression, a Cox multivariate proportional hazards regression analysis was performed with all the variables to derive risk estimates related to disease-free and overall survival and to control for confounders.
RESULTS: High NG2 expression was observed in significantly more primary tumor samples (63.6%; 84/132) compared with the adjacent noncancerous tissue samples (28.1%; 27/96) (P < 0.0001). Moreover, high NG2 protein expression was closely associated with tumor differentiation (χ2 = 9.436, P = 0.0089), recurrence (χ2 = 5.769, P = 0.0163), tumor-node-metastasis (TNM) stage (χ2 = 8.976, P = 0.0027), and invasion (χ2 = 5.476, P = 0.0193). However, no significant relationship was observed between NG2 protein expression in HCC and other parameters, such as age, sex, tumor size, serum alpha fetoprotein (AFP), tumor number, or tumor capsule. The log-rank test indicated a significant difference in the overall survival of HCC patients with high NG2 expression compared with those with low NG2 expression (29.2% vs 9.5%, P < 0.001). Moreover, NG2 expression in HCC tissue significantly correlated with disease-free survival (15.2% vs 6.7%, P < 0.001). Multivariate analysis showed that NG2 expression (HR = 2.035, P = 0.002), serum AFP (HR = 1.903, P = 0.003), TNM stage (HR = 2.039, P = 0.001), and portal vein invasion (HR = 1.938, P = 0.002) were independent prognostic indicators for OS in HCC patients. Furthermore, NG2 expression (HR = 1.974, P = 0.003), serum AFP (HR = 1.767, P = 0.008), TNM stage (HR = 2.078, P = 0.001), tumor capsule (HR = 0.652, P = 0.045), and portal vein invasion (HR = 1.941, P = 0.002) were independent prognostic indicators for DFS in HCC patients.
CONCLUSION: The up-regulation of NG2 is associated with poor prognosis in HCC. Therefore, NG2 could be useful as an additional prognostic marker to increase the resolution of traditional approaches.
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Kramann R, Dirocco DP, Maarouf OH, Humphreys BD. Matrix Producing Cells in Chronic Kidney Disease: Origin, Regulation, and Activation. CURRENT PATHOBIOLOGY REPORTS 2013; 1. [PMID: 24319648 DOI: 10.1007/s40139-013-0026-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Chronic injury to the kidney causes kidney fibrosis with irreversible loss of functional renal parenchyma and leads to the clinical syndromes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Regardless of the type of initial injury, kidney disease progression follows the same pathophysiologic processes characterized by interstitial fibrosis, capillary rarefaction and tubular atrophy. Myofibroblasts play a pivotal role in fibrosis by driving excessive extracellular matrix (ECM) deposition. Targeting these cells in order to prevent the progression of CKD is a promising therapeutic strategy, however, the cellular source of these cells is still controversial. In recent years, a growing amount of evidence points to resident mesenchymal cells such as pericytes and perivascular fibroblasts, which form extensive networks around the renal vasculature, as major contributors to the pool of myofibroblasts in renal fibrogenesis. Identifying the cellular origin of myofibroblasts and the key regulatory pathways that drive myofibroblast proliferation and transdifferentiation as well as capillary rarefaction is the first step to developing novel anti-fibrotic therapeutics to slow or even reverse CKD progression and ultimately reduce the prevalence of ESRD. This review will summarize recent findings concerning the cellular source of myofibroblasts and highlight recent discoveries concerning the key regulatory signaling pathways that drive their expansion and progression in CKD.
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Affiliation(s)
- Rafael Kramann
- Brigham and Women's Hospital, Boston, Massachusetts ; Harvard Medical School, Boston, Massachusetts ; RWTH Aachen University, Division of Nephrology, Aachen, Germany
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Reine TM, Grøndahl F, Jenssen TG, Hadler-Olsen E, Prydz K, Kolset SO. Reduced sulfation of chondroitin sulfate but not heparan sulfate in kidneys of diabetic db/db mice. J Histochem Cytochem 2013; 61:606-16. [PMID: 23757342 DOI: 10.1369/0022155413494392] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Heparan sulfate proteoglycans are hypothesized to contribute to the filtration barrier in kidney glomeruli and the glycocalyx of endothelial cells. To investigate potential changes in proteoglycans in diabetic kidney, we isolated glycosaminoglycans from kidney cortex from healthy db/+ and diabetic db/db mice. Disaccharide analysis of chondroitin sulfate revealed a significant decrease in the 4-O-sulfated disaccharides (D0a4) from 65% to 40%, whereas 6-O-sulfated disaccharides (D0a6) were reduced from 11% to 6%, with a corresponding increase in unsulfated disaccharides. In contrast, no structural differences were observed in heparan sulfate. Furthermore, no difference was found in the molar amount of glycosaminoglycans, or in the ratio of hyaluronan/heparan sulfate/chondroitin sulfate. Immunohistochemical staining for the heparan sulfate proteoglycan perlecan was similar in both types of material but reduced staining of 4-O-sulfated chondroitin and dermatan was observed in kidney sections from diabetic mice. In support of this, using qRT-PCR, a 53.5% decrease in the expression level of Chst-11 (chondroitin 4-O sulfotransferase) was demonstrated in diabetic kidney. These results suggest that changes in the sulfation of chondroitin need to be addressed in future studies on proteoglycans and kidney function in diabetes.
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Affiliation(s)
- Trine M Reine
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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Stefańska A, Stefańska AM, Péault B, Péault B, Mullins JJ, Mullins JJ. Renal pericytes: multifunctional cells of the kidneys. Pflugers Arch 2013; 465:767-73. [PMID: 23588377 DOI: 10.1007/s00424-013-1263-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2013] [Revised: 03/05/2013] [Accepted: 03/05/2013] [Indexed: 12/11/2022]
Abstract
Pericytes have become a hot topic in renal biology. They play a critical physiological role in vessel development, maintenance and remodelling through active communication with their vascular partners-endothelial cells-and modulation of extracellular matrix proteins. Multiple functions for renal pericytes have been described; specialised perivascular populations participate in glomerular filtration, regulate medullary blood flow and contribute to kidney fibrosis by differentiation into collagen-generating myofibroblasts. Interestingly, the origin of renin-producing cells of the juxtaglomerular region is attributed to the perivascular cell lineage; we have observed the coincidence of renin and pericyte marker expression during human kidney development. Finally, pericytes have been shown to share features with mesenchymal stem cells, which places them as potential renal progenitor cell candidates. Since renal diseases are often associated with microvascular complications, renal pericytes may emerge as new targets for the treatment of kidney disease.
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Affiliation(s)
- Ania Stefańska
- University/BHF Centre for Cardiovascular Science, The University of Edinburgh, Queens Medical Research Institute, 47 Little France Avenue, Edinburgh, EH16 4TJ, Scotland, UK
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Kolset SO, Reinholt FP, Jenssen T. Diabetic nephropathy and extracellular matrix. J Histochem Cytochem 2012; 60:976-86. [PMID: 23103723 DOI: 10.1369/0022155412465073] [Citation(s) in RCA: 229] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Diabetic nephropathy (DN) is a serious complication in diabetes. Major typical morphological changes are the result of changes in the extracellular matrix (ECM). Thus, basement membranes are thickened and the glomerular mesangial matrix and the tubulointerstitial space are expanded, due to increased amounts of ECM. One important ECM component, the proteoglycans (PGs), shows a more complex pattern of changes in DN. PGs in basement membranes are decreased but increased in the mesangium and the tubulointerstitial space. The amounts and structures of heparan sulfate chains are changed, and such changes affect levels of growth factors regulating cell proliferation and ECM synthesis, with cell attachment affecting endothelial cells and podocytes. Enzymes modulating heparan sulfate structures, such as heparanase and sulfatases, are implicated in DN. Other enzyme classes also modulate ECM proteins and PGs, such as matrix metalloproteinases (MMPs) and serine proteases, such as plasminogen activator, as well as their corresponding inhibitors. The levels of these enzymes and inhibitors are changed in plasma and in the kidneys in DN. Several growth factors, signaling pathways, and hyperglycemia per se affect ECM synthesis and turnover in DN. Whether ECM components can be used as markers for early kidney changes is an important research topic, whereas at present, the clinical use remains to be established.
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Affiliation(s)
- S O Kolset
- Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, Oslo, Norway.
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Abstract
Proteoglycans (PGs) impact many aspects of kidney health and disease. Models that permit genetic dissection of PG core protein and glycosaminoglycan (GAG) function have been instrumental to understanding their roles in the kidney. Matrix-associated PGs do not serve critical structural roles in the organ, nor do they contribute significantly to the glomerular barrier under normal conditions, but their abnormal expression influences fibrosis, inflammation, and progression of kidney disease. Most core proteins are dispensable for nephrogenesis (glypican-3 being an exception) and for maintenance of function in adult life, but their loss alters susceptibility to experimental kidney injury. In contrast, kidney development is exquisitely sensitive to GAG expression and fine structure as evidenced by the severe phenotypes of mutants for genes involved in GAG biosynthesis. This article reviews PG expression in normal kidney and the abnormalities caused by their disruption in mice and man.
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Affiliation(s)
- Scott J Harvey
- INSERM Avenir U983, Hôpital Necker-Enfants Malades, Paris, France
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Al-Mayhani MTF, Grenfell R, Narita M, Piccirillo S, Kenney-Herbert E, Fawcett JW, Collins VP, Ichimura K, Watts C. NG2 expression in glioblastoma identifies an actively proliferating population with an aggressive molecular signature. Neuro Oncol 2011; 13:830-45. [PMID: 21798846 PMCID: PMC3145476 DOI: 10.1093/neuonc/nor088] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2010] [Accepted: 05/13/2011] [Indexed: 12/18/2022] Open
Abstract
Glioblastoma multiforme (GBM) is the most common type of primary brain tumor and a highly malignant and heterogeneous cancer. Current conventional therapies fail to eradicate or curb GBM cell growth. Hence, exploring the cellular and molecular basis of GBM cell growth is vital to develop novel therapeutic approaches. Neuroglia (NG)-2 is a transmembrane proteoglycan expressed by NG2+ progenitors and is strongly linked to cell proliferation in the normal brain. By using NG2 as a biomarker we identify a GBM cell population (GBM NG2+ cells) with robust proliferative, clonogenic, and tumorigenic capacity. We show that a significant proportion (mean 83%) of cells proliferating in the tumor mass express NG2 and that over 50% of GBM NG2+ cells are proliferating. Compared with the GBM NG2- cells from the same tumor, the GBM of NG2+ cells overexpress genes associated with aggressive tumorigenicity, including overexpression of Mitosis and Cell Cycling Module genes (e.g., MELK, CDC, MCM, E2F), which have been previously shown to correlate with poor survival in GBM. We also show that the coexpression pattern of NG2 with other glial progenitor markers in GBM does not recapitulate that described in the normal brain. The expression of NG2 by such an aggressive and actively cycling GBM population combined with its location on the cell surface identifies this cell population as a potential therapeutic target in a subset of patients with GBM.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Colin Watts
- Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge (M.T.F.A-M., S.P., E.K-H., J.W.F., C.W.); MRC Laboratory of Molecular Biology, University of Cambridge (R.G.); CRUK Cancer Research Institute, University of Cambridge (M.N.); Division of Molecular Histopathology, Department of Pathology, University of Cambridge (V.P.C., K.I.); Department of Neurosurgery, University of Cambridge (C.W.), Cambridge, UK
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Joladarashi D, Salimath PV, Chilkunda ND. Diabetes results in structural alteration of chondroitin sulfate/dermatan sulfate in the rat kidney: effects on the binding to extracellular matrix components. Glycobiology 2011; 21:960-72. [PMID: 21406563 DOI: 10.1093/glycob/cwr029] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Chondroitin sulfate (CS)/dermatan sulfate (DS) is a group of sulfated polymers, which play an essential role in various biological phenomena. In the kidney, they are present in small but significant amounts. Studies on their structure-function relationship in the kidney and their changes during diabetic conditions have not been rigorously looked into, which is the focus of this paper. The CS/DS content decreased significantly (14%) during diabetic conditions. This was accompanied by a decrease in the CS/heparan sulfate ratio. Disaccharide composition analysis revealed fine structural changes especially with respect to the E unit [glucuronic acid β1-3 N-acetyl d-galactosamine (4,6-O-sulfate)] and the degree of sulfation. The mRNA expression levels of major enzymes involved in the synthesis of the "E"-disaccharide unit showed a decrease during diabetes. The changes in CS/DS had implications on ligand-binding properties when tested in vitro for binding to major extracellular matrix (ECM) components such as type IV collagen, laminin and fibronectin. Thus, this study provides insights into the structure-function relationship of CS/DS in the kidney during diabetes and alterations of which could aggravate conditions such as diabetic nephropathy by virtue of them being a part of ECM components.
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Affiliation(s)
- Darukeshwara Joladarashi
- Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, Karnataka, India
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Sypecka J, Sarnowska A, Domanska-Janik K. Crucial role of the local micro-environment in fate decision of neonatal rat NG2 progenitors. Cell Prolif 2009; 42:661-71. [PMID: 19614677 DOI: 10.1111/j.1365-2184.2009.00618.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVES The fate choice of neural progenitor cells could be dictated by local cellular environment of the adult CNS. The aim of our study was to investigate the effect of hippocampal tissue on differentiation and maturation of oligodendrocyte NG2 precursor cells. MATERIALS AND METHODS Hippocampal slice culture was established from the brains of 7-day-old rats. NG2 precursor cells, obtained from a 12-day-old mixed primary culture of neonatal rat cerebral hemispheres, were labelled with chloromethyl-fluorescein-diacetete and seeded on the hippocampal slices. After 7-14 days in co-culture, cells were stained with neural markers. RESULTS NG2 cells differentiated predominantly into oligodendrocytes, presenting various stages of maturation: progenitors (NG2), pre-oligodendrocytes (O4) and finally mature GalC-positive cells. However, except for a few cells with astrocyte-specific S100b staining, a considerable number of these cells differentiated into neurons: TUJ(+) and even MAP-2(+) cells were frequently observed. Moreover, a certain population of these cells preserved proliferative properties of primary precursor cells, as revealed by Ki67 expression. CONCLUSIONS The neuronal micro-environment provided by the culture of hippocampal slices is potent for induction of neurogenesis from oligodendrocyte NG2(+)/PDGFRalpha(+)/CNP(+) progenitor cells and promotes their differentiation not only into macroglia but also into neurons. It also sustains their proliferative capacity. The results indicate the crucial role of the local cellular environment in fate decision of primary NG2(+) multipotent neural progenitor cells, which may affect their behaviour after transplantation into the central nervous system.
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Affiliation(s)
- J Sypecka
- NeuroRepair Department, Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
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