Impairment of Proteasome Function in Podocytes Leads to CKD.

ABSTRACT:

Background

The ubiquitin-proteasome system (UPS) and the autophagy-lysosomal system (APLS) are major intracellular degradation procedures. The importance of the APLS in podocytes is established, but the role of the UPS is not well understood.

Methods

To investigate the role of the UPS in podocytes, mice were generated that had deletion of Rpt3 (Rpt3 ^pdKO), which encodes an essential regulatory subunit required for construction of the 26S proteasome and its deubiquitinating function.

Results

Rpt3 ^pdKO mice showed albuminuria and glomerulosclerosis, leading to CKD. Impairment of proteasome function caused accumulation of ubiquitinated proteins and of oxidative modified proteins, and it induced podocyte apoptosis. Although impai

SUBMITTER: Makino SI 

PROVIDER: S-EPMC7920174 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature