title: miR-744 enhances type I interferon signaling pathway by targeting PTP1B in primary human renal mesangial cells.
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.
authors.affiliation: Shanghai Institute of Rheumatology, Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS) &Shanghai Jiao Tong University School of Medicine (SJTUSM), Chinese Academy of Sciences (CAS), Shanghai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Shanghai Institute of Rheumatology, Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yuanjia
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Shanghai Institute of Rheumatology, Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Rheumatology, Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qu
authors.affiliation: 1] Shanghai Institute of Rheumatology, Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [2] Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS) &Shanghai Jiao Tong University School of Medicine (SJTUSM), Chinese Academy of Sciences (CAS), Shanghai, China [3] Division of Rheumatology and the Center for Autoimmune Genomics and Etiology (CAGE),Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
mesh_terms: D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D007370:Interferon Type I / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D061251:Primary Cell Culture; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D016207:Cytokines; D007370:Interferon Type I; C569733:MIRN744 microRNA, human; D035683:MicroRNAs; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1