title: miR-410 suppresses the expression of interleukin-6 as well as renal fibrosis in the pathogenesis of lupus nephritis.
abstract: Lupus nephritis (LN) is a highly complex autoimmune disease caused by systemic lupus erythematosus (SLE). MicroRNAs (miRNAs) play a vital role in the pathogenesis of SLE. Previously, a total of 29 miRNAs were identified to be down-regulated in SLE patients, in which miR-410 was likely to be involved in the signalling transduction pathways in regulating the pathogenesis of SLE. The purpose of this study was to investigate the role of miR-410 in LN and to find out whether miR-410 regulates the expression of interleukin (IL)-6 and fibrosis in LN. It was found that the expression level of miR-410 in kidney tissue of MRL/lpr mice was decreased compared to that in BALB/C mice, whereas the level of IL-6 was overexpressed in MRL/lpr mice. Luciferase assay showed that miR-410 binds directly to the 3' untranslated region (UTR) of IL-6, with the results showing that overexpression of miR-410 significantly decreased the expression level of IL-6 in SV40MES13 cells. Moreover, overexpression of miR-410 significantly reduced the expression levels of fibrosis factors such as transforming growth factor-β1 (TGF-β1) and collagen I/III in SV40MES13 cells; Inhibition of the expression of miR-410 with miR-410 inhibitor resulted in increased levels of IL-6 as well as fibrosis factors. The results identify that miR-410, as a novel and critical factor in the pathogenesis of LN, decreases IL-6 expression by binding directly to the 3'UTR and suppresses fibrosis through down-regulation of TGF-β1 in SV40MES13 cells. Our study brings new insight into understanding the complex mechanisms involved in the pathogenesis of lupus disease.
authors.affiliation: The First Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Liu
authors.affiliation: The First Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: The First Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The First Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: The First Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D015850:Interleukin-6 / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
chemical_list: D015850:Interleukin-6; D035683:MicroRNAs; D000093242:Interleukin-6 Inhibitors; C000609692:MIRN410 microRNA, mouse
keywords: Lupus nephritis (LN); MRL/lpr; SV40MES13; fibrosis; interleukin-6 (IL-6); miR-410