Jaylan Patel1, Vy Ho1, Tommy Tran1, Vikrant Rai2
1Western University of Health Sciences, 2Translational Research, Western University of Health Sciences
Objective:
To investigate the effect of hyperglycemia on neuronal repair mechanisms during wound healing by evaluating Activin A, Synaptophysin, and TNFRSF10B expression in control and diabetic rat skin tissues.
Background:
Diabetes mellitus is a leading cause of peripheral neuropathy, with progressive loss of sensory and autonomic fibers that compromise sensation and wound repair. In the peripheral nervous system, injury normally triggers axonal regeneration and synaptic remodeling. This capacity is diminished under chronic hyperglycemia. Diabetic foot ulcers (DFUs) are a debilitating complication and represent impaired neuroregeneration. Hyperglycemia’s impact on markers of nerve repair remains unclear. Activin A supports neuronal repair and extracellular matrix remodeling, Synaptophysin reflects synaptic remodeling, and TNFRSF10B mediates apoptosis and inflammation.
Design/Methods:
Skin tissues were previously collected from control and diabetic rats (n=7 each during wounding and after healing, totaling 28) for gene and protein analysis of Activin A, Synaptophysin, and TNFRSF10B using PCR and immunostaining. H&E and Trichrome staining examined skin histology. Hyperglycemia’s effect on Activin A was determined in cultured cells via immunofluorescence and PCR. Statistical significance was defined as p < 0.05.
Results:
PCR and immunostaining revealed upregulation of Activin A, Synaptophysin, and TNFRSF10B in control healed tissue versus ulcerated skin. TNFRSF10B was elevated in ulcerated diabetic skin but decreased in diabetic healed tissue versus control. Activin A and Synaptophysin were reduced in diabetic tissues before and after healing versus control. Histology showed reduced collagen in diabetic healed skin, with scar tissue without inflammation. In vitro, Activin A increased at 24 hours under hyperglycemia, then declined at 48 and 72 hours.
Conclusions:
Hyperglycemia disrupts neuronal survival, synaptic remodeling, and ECM repair, impairing wound healing in DFUs. These findings suggest neurodegeneration and dysfunctional signaling, under hyperglycemia, are a central mechanism behind poor healing in DFUs. These mediators may represent therapeutic targets to enhance nerve repair and functional recovery in diabetic neuropathy.
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