GDF11 promotes wound healing in diabetic mice via stimulating HIF-1 ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization
Acta Pharmacol Sin. 2022 Nov 8. doi: 10.1038/s41401-022-01013-2. Online ahead of print.ABSTRACTNon-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 μL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. ...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Ying Zhang Yi-Yuan Zhang Zhen-Wei Pan Qing-Qi Li Li-Hua Sun Xin Li Man-Yu Gong Xue-Wen Yang Yan-Ying Wang Hao-Dong Li Li-Na Xuan Ying-Chun Shao Meng-Meng Li Ming-Yu Zhang Qi Yu Zhange Li Xiao-Fang Zhang Dong-Hua Liu Yan-Meng Zhu Zhong-Yue Tan Yuan-Yuan Zh Source Type: research
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