Molecular mechanisms of skin wound healing in non-diabetic and diabetic mice in excision and pressure experimental wounds

• DOI: 10.1007/s00441-022-03624-x
• Publication Date: 2022-04-07T03:56:47Z
• Authors: Vito Antonio Bald...; Luca Lorenzini; Alessandro Giuliani; Maura Cescatti; Giuseppe Alastra; Micaela Pannella; Bruno Pietro Imbimbo; Gino Villetti; Laura Calzà; Luciana Giardino
• Keywords: TIMP1; Hypoxia; Hypoxia-Inducible Factors

Experimental models for chronic skin lesions are excision and pressure ulcer, defined as "open" "closed" lesions, respectively, only the latter characterized by tissue hypoxia. Moreover, systemic diseases, such diabetes mellitus, affect wound repair. Thus, testing new therapies should be carefully selected according to expected targets. In this study, we present an extensive comparative histological, immunohistochemical, molecular characterization of these two in diabetic (db/db) non-diabetic (C57BL/6 J) mice. db/db mice, found significant reduction PGP9.5-IR innervation, capillary network, reduced expression NGF receptors. We increase VEGF receptor Kdr expression, PI3K-Akt signaling pathway at core altered network. Db/db mice with ulcers showed impairment regulation hypoxia-related genes (Hif1a, Flt1, Kdr), while extracellular matrix encoding (Itgb3, Timp1, Fn1, Col4a1) were upregulated hyperglycemia lesions. Overall, analysis suggests that have a longer inflammatory phase repair process, delaying progression toward proliferation remodeling phases.