title: miR-150 promotes renal fibrosis in lupus nephritis by downregulating SOCS1.
abstract: MicroRNAs (miRs) seem to mediate renal fibrosis in several renal diseases, with some miRs having profibrotic effects and others having opposing effects. Although differential expression of certain miRs has been described in lupus nephritis, it is unknown whether miRs contribute to fibrosis or could serve as biomarkers of specific histologic manifestations of lupus nephritis. Here, we compared miR expression in kidney biopsies from patients with lupus nephritis and identified miR-150 as the most differentially expressed miR in kidneys with high chronicity (chronicity index [CI] ≥ 4); miR-150 positively correlated with chronicity scores and the expression of profibrotic proteins. Overexpression of miR-150 significantly reduced expression of the antifibrotic protein suppressor of cytokine signaling 1 (SOCS1) and upregulated profibrotic proteins in both proximal tubular and mesangial cells. Directly targeting SOCS1 with a small interfering RNA produced similar results. Furthermore, TGF-β1 induced miR-150 expression, decreased SOCS1, and increased profibrotic proteins in proximal tubular cells and podocytes; a miR-150 inhibitor reversed these changes, suggesting that the profibrotic effects of TGF-β1 are, at least in part, mediated by miR-150. Consistent with these in vitro observations, biopsies with high miR-150 and high CI exhibited substantial expression of TGF-β1, reduced SOCS1, and an increase in profibrotic proteins. In summary, miR-150 is a promising quantitative renal biomarker of kidney injury in lupus nephritis. Our results suggest that miR-150 promotes renal fibrosis by increasing profibrotic molecules through downregulation of SOCS1.
authors.affiliation: Sjögren's Syndrome Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-1190, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Sarfaraz A
authors.initials: SA
authors.lastname: Hasni
authors.forename: Paola
authors.initials: P
authors.lastname: Perez
authors.forename: Mayank
authors.initials: M
authors.lastname: Tandon
authors.forename: Shyh-Ing
authors.initials: SI
authors.lastname: Jang
authors.forename: Changyu
authors.initials: C
authors.lastname: Zheng
authors.forename: Jeffery B
authors.initials: JB
authors.lastname: Kopp
authors.forename: Howard
authors.initials: H
authors.lastname: Austin
authors.forename: James E
authors.initials: JE
authors.lastname: Balow
authors.forename: Ilias
authors.initials: I
authors.lastname: Alevizos
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Illei
mesh_terms: D015415:Biomarkers; D001706:Biopsy; D015536:Down-Regulation; D005355:Fibrosis / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C533097:MIR150, human; C108944:SOCS1 protein, human