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Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells
Background. The p38 mitogen-activated protein kinase (p38 MAPK) is an important intracellular signal transduction pathway involved in TGF-β1-induced epithelial–mesenchymal transition (EMT). Sema4C, a member of the semaphorin family, was found to be essential for the activation of p38 MAPK. However,...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070071/ https://www.ncbi.nlm.nih.gov/pubmed/20959347 http://dx.doi.org/10.1093/ndt/gfq619 |
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author | Zeng, Rui Han, Min Luo, Yun Li, Caixia Pei, Guangchang Liao, Wenhui Bai, Shoujun Ge, Shuwang Liu, XiaoCheng Xu, Gang |
author_facet | Zeng, Rui Han, Min Luo, Yun Li, Caixia Pei, Guangchang Liao, Wenhui Bai, Shoujun Ge, Shuwang Liu, XiaoCheng Xu, Gang |
author_sort | Zeng, Rui |
collection | PubMed |
description | Background. The p38 mitogen-activated protein kinase (p38 MAPK) is an important intracellular signal transduction pathway involved in TGF-β1-induced epithelial–mesenchymal transition (EMT). Sema4C, a member of the semaphorin family, was found to be essential for the activation of p38 MAPK. However, the role of Sema4C in promoting TGF-β1-induced EMT is unclear. Methods. Renal fibrosis was induced by 5/6 subtotal nephrectomy rat model. In vitro, Sema4C was induced in human proximal tubular epithelial cells (HKC) by treatment with TGF-β1, or was inhibited by siRNA or was over-expressed by Sema4C transfection. The selective p38 MAPK inhibitor, SB203580, was administered to inhibit the p38 pathway. The expression of Sema4C, the markers of EMT, p38 phosphorylation and fibronectin secretion were measured by western blotting, immunohistochemistry, immunocytochemistry or enzyme-linked immunosorbent assay. Results. The expression of Sema4C increased in HKC cells that were treated with TGF-β1. Knockdown of Sema4C potently inhibited phosphorylation of p38 MAPK and reversed TGF-β1-induced EMT. Over-expression of Sema4C via Sema4C transfection elicited p38 MAPK phosphorylation and promoted EMT. The effects of Sema4C during EMT were blocked by a p38-specific inhibitor. In vivo, the expression of Sema4C increased in the tubular epithelia of 5/6-nephrectomized rats and human fibrotic renal tissue, and similar localization of phosphorylated p38 and Sema4C was demonstrated by immunohistochemistry on serial sections. Conclusions. Our findings suggest that Sema4C plays an important role in TGF-β1-induced EMT through activation of p38 MAPK in proximal tubular epithelial cells. |
format | Text |
id | pubmed-3070071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-30700712011-04-04 Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells Zeng, Rui Han, Min Luo, Yun Li, Caixia Pei, Guangchang Liao, Wenhui Bai, Shoujun Ge, Shuwang Liu, XiaoCheng Xu, Gang Nephrol Dial Transplant Original Article Background. The p38 mitogen-activated protein kinase (p38 MAPK) is an important intracellular signal transduction pathway involved in TGF-β1-induced epithelial–mesenchymal transition (EMT). Sema4C, a member of the semaphorin family, was found to be essential for the activation of p38 MAPK. However, the role of Sema4C in promoting TGF-β1-induced EMT is unclear. Methods. Renal fibrosis was induced by 5/6 subtotal nephrectomy rat model. In vitro, Sema4C was induced in human proximal tubular epithelial cells (HKC) by treatment with TGF-β1, or was inhibited by siRNA or was over-expressed by Sema4C transfection. The selective p38 MAPK inhibitor, SB203580, was administered to inhibit the p38 pathway. The expression of Sema4C, the markers of EMT, p38 phosphorylation and fibronectin secretion were measured by western blotting, immunohistochemistry, immunocytochemistry or enzyme-linked immunosorbent assay. Results. The expression of Sema4C increased in HKC cells that were treated with TGF-β1. Knockdown of Sema4C potently inhibited phosphorylation of p38 MAPK and reversed TGF-β1-induced EMT. Over-expression of Sema4C via Sema4C transfection elicited p38 MAPK phosphorylation and promoted EMT. The effects of Sema4C during EMT were blocked by a p38-specific inhibitor. In vivo, the expression of Sema4C increased in the tubular epithelia of 5/6-nephrectomized rats and human fibrotic renal tissue, and similar localization of phosphorylated p38 and Sema4C was demonstrated by immunohistochemistry on serial sections. Conclusions. Our findings suggest that Sema4C plays an important role in TGF-β1-induced EMT through activation of p38 MAPK in proximal tubular epithelial cells. Oxford University Press 2011-04 2010-10-19 /pmc/articles/PMC3070071/ /pubmed/20959347 http://dx.doi.org/10.1093/ndt/gfq619 Text en © The Author 2011. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Zeng, Rui Han, Min Luo, Yun Li, Caixia Pei, Guangchang Liao, Wenhui Bai, Shoujun Ge, Shuwang Liu, XiaoCheng Xu, Gang Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells |
title | Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells |
title_full | Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells |
title_fullStr | Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells |
title_full_unstemmed | Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells |
title_short | Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells |
title_sort | role of sema4c in tgf-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070071/ https://www.ncbi.nlm.nih.gov/pubmed/20959347 http://dx.doi.org/10.1093/ndt/gfq619 |
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