Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds

• DOI: 10.2337/db14-0589
• Publication Date: 2014-09-04T14:16:25Z
• Authors: Fanxing Xu; Badr Othman; Jason Lim; Angelika Batres; Bhaskar Ponugoti; Chenying Zhang; Leah Yi; Jian Liu; Chen Tian; Alhassan Hameedal...; Sarah Alsadun; Rohinton Tarapore; Dana T. Graves
• Keywords: FOXO1; CCL20

Re-epithelialization is an important part in mucosal wound healing. Surprisingly little known about the impact of diabetes on molecular events We examined role transcription factor forkhead box O1 (Foxo1) oral wounds diabetic and normoglycemic mice with keratinocyte-specific Foxo1 deletion. Diabetic had significantly delayed healing reduced cell migration proliferation. deletion rescued negative but opposite effect mice. Diabetes vivo high glucose conditions vitro enhanced expression chemokine (C-C motif) ligand 20 (CCL20) interleukin-36γ (IL-36γ) a Foxo1-dependent manner. High glucose-stimulated binding to CCL20 IL-36γ promoters inhibited these cells conditions. In normal healing, was needed for transforming growth factor-β1 (TGF-β1) expression, standard conditions, TGF-β1 silencing vitro. propose that under or impairs by promoting levels enhances it inducing TGF-β1. This finding provides mechanistic insight into how mediates