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

Xiaoyan Zhang,Yuanjia Tang,Nan Shen,Xiao Han,Bo Qu,Yanfang Wu

doi:10.1038/srep12987

Abstract

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.

Highlights

Renal mesangial cells (RMCs) constitute a population of cells in glomerular mesangium
We demonstrate that miR-744 positively enhances the expression of IFN-induced genes, and that the expression of these inflammatory genes is suppressed by the inhibition of miR-744
We found that type I IFN induces miR-744 expression in RMCs. These findings suggest that miR-744 plays a vital feed-forward role in the type I IFN signaling pathway, in human RMCs, providing important information for the further investigation of the roles of miR-744 in kidney diseases associated with an over-activated type I IFN signaling pathway

Summary

Introduction

Renal mesangial cells (RMCs) constitute a population of cells in glomerular mesangium. 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. 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. RMCs play an important role in the pathogenesis of several renal diseases[1,2,3]. Another study demonstrated that the PI:C RNA/TLR3-mediated disease activity of lupus nephritis depends on activated intrinsic renal cells, such as glomerular mesangial cells, which produce cytokines (such as IFN-α ) and chemokines that aggravate autoimmune tissue injury[9]. The role of miRNAs in glomerular mesangial cells is not known

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Results

Conclusion