Targeting Src homology phosphatase 2 ameliorates mouse diabetic nephropathy by attenuating ERK/NF-κB pathway-mediated renal inflammation.

ABSTRACT: Renal inflammation is a pivotal mechanism underlying the pathophysiology of diabetic nephropathy (DN). The Src homology phosphatase 2 (SHP2) has been demonstrated to be linked to diabetes-induced inflammation, yet its roles and explicit molecular mechanisms in DN remain unexplored. Here, we report that SHP2 activity is upregulated in both DN patients and db/db mice. In addition, pharmacological inhibition of SHP2 with its specific inhibitor PHPS1 alleviates DN in db/db mice and attenuates renal inflammation. In vitro, PHPS1 administration prevents inflammatory responses in HK-2 cells stimulated by high glucose (HG). Mechanistically, PHPS1 represses HG-induced activation of the proinflammatory ERK/NF-κB signaling pathway, and these inhibitory effects are blocked in the presence of an ERK sp

SUBMITTER: Yu C 

PROVIDER: S-EPMC10729421 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature