Podocyte Integrin-β ₃ and Activated Protein C Coordinately Restrict RhoA Signaling and Ameliorate Diabetic Nephropathy.

ABSTRACT:

Background

Diabetic nephropathy (dNP), now the leading cause of ESKD, lacks efficient therapies. Coagulation protease-dependent signaling modulates dNP, in part via the G protein-coupled, protease-activated receptors (PARs). Specifically, the cytoprotective protease-activated protein C (aPC) protects from dNP, but the mechanisms are not clear.

Methods

A combination of in vitro approaches and mouse models evaluated the role of aPC-integrin interaction and related signaling in dNP.

Results

The zymogen protein C and aPC bind to podocyte integrin-β ₃, a subunit of integrin-α _v β ₃. Deficiency of this integrin impairs thrombin-mediated generation of aPC on podocytes. The interaction of aPC with integrin-

SUBMITTER: Madhusudhan T 

PROVIDER: S-EPMC7460917 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature