Downregulated MiR-206 expression promotes the proliferation and migration of macrophages by regulating IL-17A/REG3A pathway

Xuan Huang,Fang Gong,Qun Yu,Zhixian Lu,Jie Zhu

doi:10.1177/2058739220917490

Xuan Huang, Fang Gong + Show 3 more

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https://doi.org/10.1177/2058739220917490

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Abstract

This study sought to investigate the role of miR-206 in polymyositis/dermatomyositis (PM/DM) development. Transwell and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay were performed to investigate cell migration and proliferation. Real-time polymerase chain reaction (PCR) analysis was used to determine the expression of miR-206, interleukin-17A (IL-17A), IL-17 receptor A (IL-17RA), and regenerating islet-derived protein 3-alpha (REG3A). Significantly, miR-206 mimics decreased macrophage migration and proliferation, while miR-206 inhibitors exhibited the opposite effects. Indeed, elevating IL-17RA levels resulted in increased REG3A expression, which was inhibited by IL-17RA siRNA. Besides, miR-206 mimics decreased IL-17A and REG3A expressions, but miR-206 inhibitors showed opposite effects. Moreover, miR-206 expression in PM/DM patients was significantly reduced compared with the healthy controls, while IL-17A and REG3A expressions substantially increased among PM/DM patients. These findings suggested that downregulation of miR-206 increased the migration and proliferation of macrophages via IL-17A/REG3A signaling pathway, which could promote the inflammatory infiltration in PM/DM.

Highlights

Polymyositis/dermatomyositis (PM/DM), a systemic inflammatory disorder, can affect organs such as skeletal muscles and skin, which is characterized by symmetric proximal muscle weakness and elevated serum muscle enzymes.[1]
Macrophages were treated with different concentrations of IL-17A (R&D Systems, Minneapolis, MN, USA), and the result showed that Regenerating islet-derived protein 3-alpha (REG3A) expression was elevated at increased IL-17A concentration with its strongest expression achieved at
When macrophages were treated with siRNA targeting IL-17 receptor A (IL-17RA), the expression of REG3A induced by IL-17A was inhibited (Figure 1(b))

Summary

Introduction

Polymyositis/dermatomyositis (PM/DM), a systemic inflammatory disorder, can affect organs such as skeletal muscles and skin, which is characterized by symmetric proximal muscle weakness and elevated serum muscle enzymes.[1]. Regenerating islet-derived protein 3-alpha (REG3A) is an antimicrobial protein which controls bacteria proliferation.[3,4] existing literature supports that the induction of REG3A by interleukin17A (IL-17A) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) could facilitate proliferation of skin keratinocyte.[5] the role of REG3A in PM/DM pathogenesis is unclear. In this regard, this study aims to investigate the role of IL-17A and REG3A in PM/DM.

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