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Updated: May 10, 2026
Delivery of Exogenous Artificially Synthesized miRNA Mimic to the Kidney Using Polyethylenimine Nanoparticles in Several Kidney Disease Mouse Models
Published on: May 10, 2022
miR-150 promotes renal fibrosis in lupus nephritis by downregulating SOCS1
Hua Zhou1, Sarfaraz A Hasni, Paola Perez
1Sjögren's Syndrome Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-1190, USA.
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.
Insights
MicroRNAs (miRs) like miR-150 are implicated in lupus nephritis fibrosis. This study identifies miR-150 as a biomarker for kidney injury, promoting fibrosis by downregulating SOCS1.
Area of Science:
- Nephrology
- Molecular Biology
- Immunology
Background:
- MicroRNAs (miRs) play roles in renal fibrosis, but their specific contribution to lupus nephritis (LN) and potential as biomarkers remain unclear.
- Understanding miR involvement is crucial for diagnosing and treating LN-associated kidney damage.
Purpose of the Study:
- To investigate the role of miRs in renal fibrosis in lupus nephritis.
- To identify specific miRs that correlate with histologic damage and profibrotic markers.
- To explore the mechanistic link between miR-150, SOCS1, and TGF-β1 in kidney fibrosis.
Main Methods:
- Compared miR expression in kidney biopsies from lupus nephritis patients with varying chronicity.
- Utilized cell culture models (proximal tubular cells, mesangial cells, podocytes) to study miR-150 function.
- Employed techniques like small interfering RNA (siRNA) and miR inhibitors to elucidate molecular pathways.
- Correlated miR-150 levels with chronicity index (CI) and profibrotic protein expression in patient biopsies.
Main Results:
- miR-150 was identified as the most differentially expressed miR in lupus nephritis kidneys with high chronicity (CI ≥ 4).
- miR-150 expression positively correlated with CI and profibrotic protein levels.
- Overexpression of miR-150 reduced antifibrotic SOCS1 and increased profibrotic markers; targeting SOCS1 mimicked these effects.
- TGF-β1 induced miR-150, decreased SOCS1, and increased profibrotic proteins, effects reversed by a miR-150 inhibitor, indicating TGF-β1's profibrotic action is partly mediated by miR-150.
- High miR-150 and CI in biopsies correlated with high TGF-β1, reduced SOCS1, and increased profibrotic proteins.
Conclusions:
- miR-150 is a promising quantitative biomarker for kidney injury in lupus nephritis.
- miR-150 promotes renal fibrosis by upregulating profibrotic molecules via SOCS1 downregulation.
- These findings elucidate a novel mechanism in lupus nephritis pathogenesis and suggest therapeutic targets.
