Analytical Cellular Pathology (Jan 2020)

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

  • Jun Hong,
  • Bang-Chuan Hu,
  • Liang Xu,
  • Yang Zheng,
  • Zi-Qiang Shao,
  • Run Zhang,
  • Xiang-Hong Yang,
  • Ren-Hua Sun,
  • Shi-Jing Mo

DOI
https://doi.org/10.1155/2020/2894650
Journal volume & issue
Vol. 2020

Abstract

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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.