Biphasic Regulation of HMG-CoA Reductase Expression and Activity During Wound Healing and Its Functional Role in the Control of Keratinocyte Angiogenic and Proliferative Responses

This study examined the role of HMG-CoA reductase (HMGR) in wound healing in mice, revealing a biphasic increase in HMGR expression and activity post-wounding, with peaks at days 3 and 13. Keratinocytes at wound margins were identified as a source of HMGR expression. Growth factors like EGF and insulin co-induced HMGR activity and VEGF expression in keratinocytes. Simvastatin, an HMGR inhibitor, reduced insulin-induced VEGF expression and keratinocyte proliferation, effects reversible by mevalonate. In vivo, simvastatin disrupted keratinocyte proliferation and reduced VEGF expression, impairing wound healing. The study highlighted HMGR's role in keratinocyte angiogenic and proliferative responses, suggesting its importance in skin repair processes.