MicroRNA-19a Targets Fibroblast Growth Factor-Inducible Molecule 14 and Prevents Tubular Damage in Septic AKI

Anal Cell Pathol (Amst). 2020 Jul 1:2020:2894650. doi: 10.1155/2020/2894650. eCollection 2020.

Abstract

Fibroblast growth factor-inducible molecule 14 (Fn14) plays a principal role in triggering tubular damage during septic acute kidney injury (AKI). Here, we explore the mechanism underlying Fn14 deregulation in septic AKI. We identify Fn14 as a bona fide target of miR-19a, which directly binds to 3' UTR of Fn14 for repression independent of cylindromatosis (CYLD), the deubiquitinase (DUB) downstream of miR-19a, and thereby antagonizes the LPS-induced tubular cell apoptosis. Genetic ablation of Fn14, but not of CYLD, abolishes the ability of miR-19a to antagonize the tubular apoptosis by lipopolysaccharide (LPS). In mice, systemic delivery of miR-19a confers protection against septic AKI. Our findings implicate that miR-19a may serve as a promising therapeutic candidate in the prevention of septic AKI.

MeSH terms

  • Acute Kidney Injury / complications*
  • Acute Kidney Injury / prevention & control
  • Animals
  • Apoptosis
  • Base Sequence
  • Deubiquitinating Enzyme CYLD / metabolism
  • Kidney Tubules / pathology*
  • Lipopolysaccharides
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RAW 264.7 Cells
  • Sepsis / complications*
  • Sepsis / prevention & control
  • TWEAK Receptor / genetics
  • TWEAK Receptor / metabolism*

Substances

  • Lipopolysaccharides
  • MIRN19 microRNA, mouse
  • MicroRNAs
  • TWEAK Receptor
  • CYLD protein, mouse
  • Deubiquitinating Enzyme CYLD