NMDA receptor-mediated CaMKII/ERK activation contributes to renal fibrosis.

ABSTRACT:

Background

This study aimed to understand the mechanistic role of N-methyl-D-aspartate receptor (NMDAR) in acute fibrogenesis using models of in vivo ureter obstruction and in vitro TGF-β administration.

Methods

Acute renal fibrosis (RF) was induced in mice by unilateral ureteral obstruction (UUO). Histological changes were observed using Masson's trichrome staining. The expression levels of NR1, which is the functional subunit of NMDAR, and fibrotic and epithelial-to-mesenchymal transition markers were measured by immunohistochemical and Western blot analysis. HK-2 cells were incubated with TGF-β, and NMDAR antagonist MK-801 and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) antagonist KN-93 were administered for pathway determination. Chronic RF was introd

SUBMITTER: Zhou J 

PROVIDER: S-EPMC7488001 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature