MiR-152 Attenuates the Severity of Lupus Nephritis Through the Downregulation of Macrophage Migration Inhibitory Factor (MIF)-Induced Expression of COL1A1.

Jiayi Zheng,Yang Song,Ruru Guo,Jie Chen,Yuanjia Tang,Richard Bucala,Qiong Fu,Lin Leng,Lingling Wu,Liangjing Lu

doi:10.3389/fimmu.2019.00158

Jiayi Zheng, Yang Song + Show 8 more

Open Access

https://doi.org/10.3389/fimmu.2019.00158

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Abstract

Background: The role of miR-152 in lupus nephritis has not been elucidated. The aim of this study was to investigate the role of miR-152 in the pathogenesis of lupus nephritis (LN).Methods: miR-152 expression was detected using RT-PCR in LN tissue and normal controls. The miR-152 expression was compared with clinical parameters such as 24 h urine protein excretion level, serum creatinine, and serum complement level and SLEDAI score. The function of miR-152 was examined using human renal proximal tubular epithelial cells (HRPTE). miR-152 mimics and inhibitors were transfected to HRPTEs to ascertain the effects of miR-152.Results: miR-152 expression was downregulated in LN tissue. There was an inverse correlation between miR-152 expression in LN tissue and clinical parameters like 24 h urine protein excretion levels and serum creatinine, but not serum complement levels or SLEDAI. Further analysis showed that macrophage migration inhibitory factor (MIF) was a direct target of miR-152. Downregulation of MIF through complementary binding of miR-152 inhibited the renal expression of COL1A1.Conclusion: miR-152 expression was tapered in LN tissue and miR-152 expression was inversely correlated with chronicity index (CI), serum creatinine and severity of proteinuria. miR-152 may attenuate the severity of LN through the downregulation of MIF-induced expression of COL1A1. These findings suggest that miR-152 may be a potential target for the treatment of LN.

Highlights

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder that typically affects women of childbearing age
We found that reduced miR-152 expression in lupus nephritis (LN) tissue was associated with higher chronicity indices (CI) on histopathological examination, higher serum creatinine levels, and higher 24 h urine protein excretion levels in LN patients
Using Austin activity indices and chronicity indices, we found that levels of miR152 expression correlated with the chronicity indices on renal biopsy (r = −0.4737, p = 0.0259)

Summary

Introduction

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder that typically affects women of childbearing age. It is characterized by a loss of immune tolerance and production of autoantibodies. Renal involvement occurs in over 60% of patients miR-152 Attenuates LN Through MIF Inhibition with SLE and is a strong predictor of morbidity and mortality [1]. Current treatment of LN includes immunosuppressive agents such as cyclophosphamide and mycophenolate mofetil. Non-specific immunosuppression often leads to a variety of adverse effects, and we feel the need to explore effective targeted medication. The role of miR-152 in lupus nephritis has not been elucidated. The aim of this study was to investigate the role of miR-152 in the pathogenesis of lupus nephritis (LN)

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