TYRO3 protects podocyte via JNK/c-jun-P53 pathway

Arch Biochem Biophys. 2023 May 1:739:109578. doi: 10.1016/j.abb.2023.109578. Epub 2023 Mar 21.

Abstract

Podocyte injury plays a critical role in diabetic kidney disease (DKD). Our previous work demonstrated a protective role of tyrosine-protein kinase receptor TYRO3 in glomerular disease; However, the downstream signaling of TYRO3 remains unclear. Our data showed that genetic ablation of tyro3 in zebrafish recapitulated a nephrotic syndrome phenotype. TYRO3 expression was suppressed by high glucose and TGF-β, which may contribute to the decreased TYRO3 expression in progressive DKD. Moreover, knockdown of TYRO3 expression with siRNA induced podocytes apoptosis and cytoskeleton rearrangement. Further study revealed that TYRO3 conferred antiapoptotic effects through the activation of JNK/c-jun-P53 in podocytes. Our results revealed a novel signaling module of TYRO3 in podocyte homeostasis, which provides a new molecular insight of TYRO3 effect in podocyte protection.

Keywords: Diabetic kidney disease; Podocyte; TYRO3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Diabetic Nephropathies* / genetics
  • Diabetic Nephropathies* / metabolism
  • Podocytes* / metabolism
  • Signal Transduction
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Zebrafish / metabolism

Substances

  • Tumor Suppressor Protein p53