PloS one
TRPM7 modulates endothelial cell functions and VEGFA-associated signaling in diabetic foot
By Cheng Y, Jia L, Sheng L and 2 others.
Abstract
Background
Endothelial dysfunction is a central contributor to the development of diabetic foot complications. However, the regulatory mechanisms underlying impaired vascular endothelial cell (VEC) function in diabetic foot remain incompletely understood. Transient Receptor Potential Melastatin 7 (TRPM7) is implicated in cardiovascular pathology, yet its role in diabetic foot-related endothelial impairment is unclear.
Methods
Primary VECs were isolated from foot vascular tissues obtained from control participants and patients with DFUs and identified by CD31 and factor VIII immunofluorescence. Proliferation, apoptosis, migration, and in vitro tube formation were quantitatively assessed. TRPM7 was overexpressed in control-derived VECs and knocked down using shRNA in DFU-derived VECs. TRPM7 expression and VEGFA-AKT-ERK-related proteins were evaluated using RT-qPCR and Western blotting. Advanced glycation end products (AGEs) and inducible nitric oxide synthase (iNOS) concentrations in conditioned culture supernatants were measured by ELISA.