In primary vascular endothelial cells from diabetic foot ulcer patients, higher TRPM7 expression was associated with impaired proliferation, migration, tube formation and increased apoptosis, and TRPM7 manipulation was accompanied by changes in VEGFA-AKT-ERK-related signaling, supporting TRPM7 as a candidate regulator of endothelial dysfunction under diabetic-foot-related conditions.
Vascular endothelial cells (VECs) derived from diabetic foot ulcer (DFU) tissue showed functional impairment compared with control-derived VECs.
Conditioned supernatants from DFU-derived VECs contained higher concentrations of AGEs and iNOS protein than those from control-derived VECs.
TRPM7 expression was higher in DFU-derived VECs than in control-derived VECs.
TRPM7 overexpression in control-derived VECs induced a dysfunctional cellular phenotype.
TRPM7 knockdown in DFU-derived VECs partially restored endothelial function and reduced apoptosis.
TRPM7 manipulation was accompanied by changes in VEGFA expression and AKT and ERK phosphorylation.
The authors conclude that TRPM7 is a candidate regulator of endothelial dysfunction under diabetic-foot-related conditions.
This study looked at the cells lining blood vessels (endothelial cells) taken from the feet of people with diabetic foot ulcers and from control participants. Cells from ulcer patients grew and moved less, formed fewer new vessel-like tubes in the lab, and died more often. Their culture fluid also had higher levels of two harmful markers, AGEs and iNOS. The researchers found that a channel protein called TRPM7 was higher in cells from diabetic foot ulcers. Raising TRPM7 in control cells made them behave like the damaged cells, while lowering it in ulcer-derived cells partly restored growth, movement and tube formation and reduced cell death. These changes went along with shifts in VEGFA and in the AKT and ERK signaling pathways, which are involved in blood vessel growth. This research suggests TRPM7 may be involved in the blood vessel damage seen in diabetic foot problems and could be a target for future study. The work was done in cultured cells, and the signaling findings are associations, so it does not show whether altering TRPM7 would help patients.
Cheng Y, Jia L, Sheng L, Han X, Zhao Y. (2026). TRPM7 modulates endothelial cell functions and VEGFA-associated signaling in diabetic foot.. PloS one. https://doi.org/10.1371/journal.pone.0359834