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miR-141 regulates TGF-β1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells
Epithelial-mesenchymal transition (EMT) plays a critical role in embryonic development, wound healing, tissue regeneration, cancer progression and organ fibrosis. The proximal tubular epithelial cells undergo EMT, resulting in matrix-producing fibroblasts and thereby contribute to the pathogenesis o...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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D.A. Spandidos
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292766/ https://www.ncbi.nlm.nih.gov/pubmed/25421593 http://dx.doi.org/10.3892/ijmm.2014.2008 |
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author | HUANG, YUANHANG TONG, JUNRONG HE, FENG YU, XINPEI FAN, LIMING HU, JING TAN, JIANGPING CHEN, ZHENGLIANG |
author_facet | HUANG, YUANHANG TONG, JUNRONG HE, FENG YU, XINPEI FAN, LIMING HU, JING TAN, JIANGPING CHEN, ZHENGLIANG |
author_sort | HUANG, YUANHANG |
collection | PubMed |
description | Epithelial-mesenchymal transition (EMT) plays a critical role in embryonic development, wound healing, tissue regeneration, cancer progression and organ fibrosis. The proximal tubular epithelial cells undergo EMT, resulting in matrix-producing fibroblasts and thereby contribute to the pathogenesis of renal fibrosis. The profibrotic cytokine, TGF-β, is now recognized as the main pathogenic driver that has been shown to induce EMT in tubular epithelial cells. Increasing evidence indicate that HIPK2 dysfunction may play a role in fibroblasts behavior, and therefore, HIPK2 may be considered as a novel potential target for anti-fibrosis therapy. Recently, members of the miR-200 family (miR-200a, b and c and miR-141) have been shown to inhibit EMT. However, the steps of the multifactorial renal fibrosis progression that these miRNAs regulate, particularly miR-141, are unclear. To study the functional importance of miR-141 in EMT, a well-established in vitro EMT assay was used to demonstrate renal tubulointerstitial fibrosis; transforming growth factor-β1-induced EMT in HK-2 cells. Overexpression of miR-141 in HK-2 cells, either with or without TGF-β1 treatment, hindered EMT by enhancing E-cadherin and decreasing vimentin and fibroblast-specific protein 1 expression. miR-141 expression was repressed during EMT in a dose- and time-dependent manner through upregulation of HIPK2 expression. Ectopic expression of HIPK2 promoted EMT by decreasing E-cadherin. Furthermore, co-transfection of miR-141 with the HIPK2 ORF clone partially inhibited EMT by restoring E-cadherin expression. miR-141 downregulated the expression of HIPK2 via direct interaction with the 3′-untranslated region of HIPK2. Taken together, these findings aid in the understanding of the role and mechanism of miR-141 in regulating renal fibrosis via the TGF-β1/miR-141/HIPK2/EMT axis, and miR-141 may represent novel biomarkers and therapeutic targets in the treatment of renal fibrosis. |
format | Online Article Text |
id | pubmed-4292766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-42927662016-02-01 miR-141 regulates TGF-β1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells HUANG, YUANHANG TONG, JUNRONG HE, FENG YU, XINPEI FAN, LIMING HU, JING TAN, JIANGPING CHEN, ZHENGLIANG Int J Mol Med Articles Epithelial-mesenchymal transition (EMT) plays a critical role in embryonic development, wound healing, tissue regeneration, cancer progression and organ fibrosis. The proximal tubular epithelial cells undergo EMT, resulting in matrix-producing fibroblasts and thereby contribute to the pathogenesis of renal fibrosis. The profibrotic cytokine, TGF-β, is now recognized as the main pathogenic driver that has been shown to induce EMT in tubular epithelial cells. Increasing evidence indicate that HIPK2 dysfunction may play a role in fibroblasts behavior, and therefore, HIPK2 may be considered as a novel potential target for anti-fibrosis therapy. Recently, members of the miR-200 family (miR-200a, b and c and miR-141) have been shown to inhibit EMT. However, the steps of the multifactorial renal fibrosis progression that these miRNAs regulate, particularly miR-141, are unclear. To study the functional importance of miR-141 in EMT, a well-established in vitro EMT assay was used to demonstrate renal tubulointerstitial fibrosis; transforming growth factor-β1-induced EMT in HK-2 cells. Overexpression of miR-141 in HK-2 cells, either with or without TGF-β1 treatment, hindered EMT by enhancing E-cadherin and decreasing vimentin and fibroblast-specific protein 1 expression. miR-141 expression was repressed during EMT in a dose- and time-dependent manner through upregulation of HIPK2 expression. Ectopic expression of HIPK2 promoted EMT by decreasing E-cadherin. Furthermore, co-transfection of miR-141 with the HIPK2 ORF clone partially inhibited EMT by restoring E-cadherin expression. miR-141 downregulated the expression of HIPK2 via direct interaction with the 3′-untranslated region of HIPK2. Taken together, these findings aid in the understanding of the role and mechanism of miR-141 in regulating renal fibrosis via the TGF-β1/miR-141/HIPK2/EMT axis, and miR-141 may represent novel biomarkers and therapeutic targets in the treatment of renal fibrosis. D.A. Spandidos 2015-02 2014-11-24 /pmc/articles/PMC4292766/ /pubmed/25421593 http://dx.doi.org/10.3892/ijmm.2014.2008 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles HUANG, YUANHANG TONG, JUNRONG HE, FENG YU, XINPEI FAN, LIMING HU, JING TAN, JIANGPING CHEN, ZHENGLIANG miR-141 regulates TGF-β1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells |
title | miR-141 regulates TGF-β1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells |
title_full | miR-141 regulates TGF-β1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells |
title_fullStr | miR-141 regulates TGF-β1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells |
title_full_unstemmed | miR-141 regulates TGF-β1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells |
title_short | miR-141 regulates TGF-β1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells |
title_sort | mir-141 regulates tgf-β1-induced epithelial-mesenchymal transition through repression of hipk2 expression in renal tubular epithelial cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292766/ https://www.ncbi.nlm.nih.gov/pubmed/25421593 http://dx.doi.org/10.3892/ijmm.2014.2008 |
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