Effects of PARP1 inhibitor PJ-34 on TGFα, IL-6, and IL-1β levels in diabetic nephropathy.

Abstract

Diabetic nephropathy is a severe chronic complication characterized by cytotoxicity, inflammation, and fibrosis, ultimately leading to renal failure. This study systematically investigated the effects of the PARP1 inhibitor PJ-34 on high glucose-induced cytotoxicity, inflammation, and fibrosis in HK-2 cells, as well as its improvement on neuropathic pain response and transforming growth factor β (TGFβ) expression in a type 1 diabetes mellitus diabetic nephropathy mouse model. Through cellular and animal experiments, we observed that PJ-34 significantly enhanced the proliferative capacity of cells damaged by high glucose, reduced apoptosis, and decreased the release of proinflammatory factors TGFα, interleukin-6, and interleukin-1β. In the type 1 diabetes mellitus nephropathy mouse model, the administration of PJ-34 substantially improved parameters of neuropathic pain, alleviated renal tissue damage, reduced indicators of renal functional impairment-inhibited renal fibrosis, and reduced the key protein expression in the epithelial-mesenchymal transition process, acting through the regulation of the TGFβ/Smads signaling pathway. This study elucidated the mechanism of action of the PARP1 inhibitor PJ-34 as a potential therapeutic agent for diabetic nephropathy, offering a novel strategy for its treatment.