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miR-744 enhances type I interferon signaling pathway by targeting PTP1B in primary human renal mesangial cells

Renal mesangial cells (RMCs) constitute a population of cells in glomerular mesangium. Inflammatory cytokines produced by RMCs play a vital role in renal inflammation. miRNAs are key regulators of inflammatory cytokine expression. The abnormal expression of renal miRNAs and the consequent changes in...

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Autores principales: Zhang, Xiaoyan, Han, Xiao, Tang, Yuanjia, Wu, Yanfang, Qu, Bo, Shen, Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531339/
https://www.ncbi.nlm.nih.gov/pubmed/26259828
http://dx.doi.org/10.1038/srep12987
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author Zhang, Xiaoyan
Han, Xiao
Tang, Yuanjia
Wu, Yanfang
Qu, Bo
Shen, Nan
author_facet Zhang, Xiaoyan
Han, Xiao
Tang, Yuanjia
Wu, Yanfang
Qu, Bo
Shen, Nan
author_sort Zhang, Xiaoyan
collection PubMed
description Renal mesangial cells (RMCs) constitute a population of cells in glomerular mesangium. Inflammatory cytokines produced by RMCs play a vital role in renal inflammation. miRNAs are key regulators of inflammatory cytokine expression. The abnormal expression of renal miRNAs and the consequent changes in inflammatory signal transduction are closely associated with renal inflammation. However, our knowledge of the functions of renal miRNAs is still limited. In this study, we investigated the role of miR-744 in type I interferon (IFN) signaling pathway in primary human RMCs. We show that overexpression of miR-744 enhances IFN-induced CCL2, CCL5, CXCL10, and IL6 expression specifically in RMCs. We found that the activation of TYK2, STAT1 and STAT3 was significantly enhanced by miR-744. miR-744 also enhanced the activation of non-classical signal components, such as ERK and p38. We then identified PTP1B, a ubiquitously expressed phosphatase, as the target of miR-744 that is responsible for enhancing type I IFN response. Finally, miR-744 expression was induced by type I IFN in RMCs. Collectively, our data indicate that by targeting PTP1B, miR-744 plays a feed-forward role in regulating type I IFN signaling pathway. These findings give us new insights into the functions of renal miRNAs in regulating important signaling pathways.
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spelling pubmed-45313392015-08-12 miR-744 enhances type I interferon signaling pathway by targeting PTP1B in primary human renal mesangial cells Zhang, Xiaoyan Han, Xiao Tang, Yuanjia Wu, Yanfang Qu, Bo Shen, Nan Sci Rep Article Renal mesangial cells (RMCs) constitute a population of cells in glomerular mesangium. Inflammatory cytokines produced by RMCs play a vital role in renal inflammation. miRNAs are key regulators of inflammatory cytokine expression. The abnormal expression of renal miRNAs and the consequent changes in inflammatory signal transduction are closely associated with renal inflammation. However, our knowledge of the functions of renal miRNAs is still limited. In this study, we investigated the role of miR-744 in type I interferon (IFN) signaling pathway in primary human RMCs. We show that overexpression of miR-744 enhances IFN-induced CCL2, CCL5, CXCL10, and IL6 expression specifically in RMCs. We found that the activation of TYK2, STAT1 and STAT3 was significantly enhanced by miR-744. miR-744 also enhanced the activation of non-classical signal components, such as ERK and p38. We then identified PTP1B, a ubiquitously expressed phosphatase, as the target of miR-744 that is responsible for enhancing type I IFN response. Finally, miR-744 expression was induced by type I IFN in RMCs. Collectively, our data indicate that by targeting PTP1B, miR-744 plays a feed-forward role in regulating type I IFN signaling pathway. These findings give us new insights into the functions of renal miRNAs in regulating important signaling pathways. Nature Publishing Group 2015-08-11 /pmc/articles/PMC4531339/ /pubmed/26259828 http://dx.doi.org/10.1038/srep12987 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhang, Xiaoyan
Han, Xiao
Tang, Yuanjia
Wu, Yanfang
Qu, Bo
Shen, Nan
miR-744 enhances type I interferon signaling pathway by targeting PTP1B in primary human renal mesangial cells
title miR-744 enhances type I interferon signaling pathway by targeting PTP1B in primary human renal mesangial cells
title_full miR-744 enhances type I interferon signaling pathway by targeting PTP1B in primary human renal mesangial cells
title_fullStr miR-744 enhances type I interferon signaling pathway by targeting PTP1B in primary human renal mesangial cells
title_full_unstemmed miR-744 enhances type I interferon signaling pathway by targeting PTP1B in primary human renal mesangial cells
title_short miR-744 enhances type I interferon signaling pathway by targeting PTP1B in primary human renal mesangial cells
title_sort mir-744 enhances type i interferon signaling pathway by targeting ptp1b in primary human renal mesangial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531339/
https://www.ncbi.nlm.nih.gov/pubmed/26259828
http://dx.doi.org/10.1038/srep12987
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