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

Front Immunol. 2019 Feb 6:10:158. doi: 10.3389/fimmu.2019.00158. eCollection 2019.

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.

Keywords: COL1A1; chronicity index; lupus nephritis; macrophage migration inhibitory Factor (MIF); miR-152.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Biopsy
  • Collagen Type I / genetics*
  • Collagen Type I, alpha 1 Chain
  • Gene Expression Regulation*
  • Humans
  • Intramolecular Oxidoreductases / metabolism*
  • Lupus Nephritis / diagnosis
  • Lupus Nephritis / genetics*
  • Lupus Nephritis / metabolism*
  • Macrophage Migration-Inhibitory Factors / metabolism*
  • MicroRNAs / genetics*
  • RNA Interference*
  • RNA, Messenger / genetics
  • Severity of Illness Index

Substances

  • 3' Untranslated Regions
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • MIRN152 microRNA, human
  • Macrophage Migration-Inhibitory Factors
  • MicroRNAs
  • RNA, Messenger
  • Intramolecular Oxidoreductases
  • MIF protein, human