A Brief Overview about MAPK14 Gene Association with Diabetic Foot Ulcers

Abstract

Diabetic foot ulcer (DFU) is a leading cause of morbidity and mortality associated with significant healthcare costs. Along with a life-time risk of up to 25%, DFUs account for approximately 25% of all hospital stays for patients with diabetes and about two-thirds of all nontraumatic amputations performed. Epidemiological studies have suggested multiple risk factors for DFUs: diabetic neuropathy, peripheral vascular disease, biomechanical factors, previous foot ulceration, poor glycaemic control, longer duration of diabetes, smoking, ethnicity, retinopathy, nephropathy, insulin use, poor vision, age and male sex. MAPK14 encodes p38α mitogen-activated protein kinase (MAPK) which is the prototypic member of the p38 MAPK family. p38 MAPKs are also known as stress-activated serine/threonine-specific kinases (SAPKs). In addition to MAPK14 for p38α MAPK, the p38 MAPK family has three additional members, including MAPK11, MAPK12 and MAPK13 which encodes p38β MAPK, p38γ MAPK and p38δ MAPK isoforms, respectively. p38α MAPK was originally identified as a tyrosine phosphorylated protein detected in activated immune cell macrophages with an essential role in inflammatory cytokine induction, such as Tumor Necrotic Factor α (TNFα). 6 Thereby, the MAPK14 protein is also implicated to affect wound healing, while its specific function appears to depend on cell type as well as exogenous and endogenous stimuli.