The PKM2 activator TEPP-46 suppresses kidney fibrosis via inhibition of the EMT program and aberrant glycolysis associated with suppression of HIF-1α accumulation.

ABSTRACT:

Aims/introduction

Tubulointerstitial fibrosis is a hallmark of diabetic nephropathy and is associated with an epithelial-to-mesenchymal transition (EMT) program and aberrant glycolysis. Dimeric pyruvate kinase (PK) M2 (PKM2) acts as a key protein kinase in aberrant glycolysis by promoting the accumulation of hypoxia-inducible factor (HIF)-1α, while tetrameric PKM2 functions as a pyruvate kinase in oxidative phosphorylation. The aim of the research is to study the effect of PKM2 tetramer activation on preventing kidney fibrosis via suppression of aberrant glycolysis and the EMT program.

Materials and methods

In vivo: Streptozotocin (STZ) was utilized to induce diabetes in 8-week-old CD-1 mice; 4 weeks after diabetes induction, proteinuria-induced kidney fibrosis was developed

SUBMITTER: Liu H 

PROVIDER: S-EPMC8089020 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature