790 Chronic skin wounds of genetically modified (db/db) and diet-induced diabetic mice have altered levels of TSG-6 and TSP-1

Chronic non-healing wounds are a major complication of diabetes. Effective communication between immune cells and the extracellular matrix (ECM) is crucial for regulating wound healing. Tumor necrosis factor-stimulated gene-6 (TSG-6) modifies regulates inflammation; Thrombospondin 1 (TSP-1) angiogenesis binds to TSG-6. In both TSG-6 TSP-1 knockout mice, closure delayed. We hypothesize that hyperglycemia causes dysregulation TSP-1, which together results in fewer heavy chain-hyaluronan complexes (HC-HA) ECM, an acceleration leukocyte infiltration, pro-inflammatory milieu, healing delay. this study, was examined multiple diabetic models. Our diet-induced model novel resembles human diabetes terms endocrine dysfunction delayed Feeding mice high-fat diet (HFD) 8 months failed generate or cause The then modified by adding low dose streptozotocin (STZ) injections, testing various factors arrive at successful HFD+STZ protocol rendered animals but still able survive stress wounding. showed higher body weights serum glucose levels than on normal (p= 0.015, p=0.004 respectively; n=6). Wound group day 5 post wounding (p=0.0018).Tissues were analyzed TSG-6, anti-inflammatory cytokines, markers using western blot qPCR. Both db/db models lower TSP-1. Understanding link hyperglycemia-induced alterations persistent inflammation may help direct development therapeutic agent prevent manage wounds.