Topical GDF11 accelerates skin wound healing in both type 1 and 2 diabetic mouse models

• Published in: Biochemical and biophysical research communications Vol. 529; no. 1; pp. 7 - 14
• Main Authors: Li, Qingqi, Jiao, Lei, Shao, Yingchun, Li, Mengmeng, Gong, Manyu, Zhang, Yuanyuan, Tan, Zhongyue, Wang, Yanying, Yang, Xuewen, Wang, Zhiguo, Zhang, Ying
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.08.2020
• Subjects: Administration, Topical; Animals; Apoptosis - drug effects; Apoptosis - physiology; Bone Morphogenetic Proteins - administration & dosage; Bone Morphogenetic Proteins - physiology; Cell Proliferation - drug effects; Cell Proliferation - physiology; Cells, Cultured; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - pathology; Diabetes Mellitus, Type 2 - physiopathology; Fibroblasts - drug effects; Fibroblasts - pathology; Fibrosis; Growth differentiation factor 11; Growth Differentiation Factors - administration & dosage; Growth Differentiation Factors - physiology; High glucose; Hippo pathway; Humans; Male; Mice; Mice, Inbred C57BL; Signal Transduction - drug effects; Signal Transduction - physiology; Skin - drug effects; Skin - injuries; Skin - pathology; Skin wound healing; Wound Healing - drug effects; Wound Healing - physiology; Growth differentiation factor 11; Skin wound healing; Hippo pathway; Diabetes mellitus; Fibrosis; High glucose
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.05.036

This study aimed to investigate the role of truncated growth differentiation factor 11 (GDF11), in which the recognition site of Furin from wild-type GDF11 was deleted to enhance the cellular stability, in skin wound healing in the setting of diabetes mellitus (DM) and the underlying mechanisms. Our study found that both truncated and natural GDF11s effectively accelerated wound healing processes in both T1DM and T2DM mice with a potency compatible to PDGF, bFGF, and EGF, but being much higher than GDF8. At the cellular level, GDF11 stimulated the proliferation and suppressed HG-induced apoptosis of HSFs. Further study revealed that GDF11 activated the YAP—Smad2/3—CTGF fibrotic signaling pathway by reversing HG-induced upregulation of phosphorylated form of YAP (p-YAP), increases p-Smad2/3 levels, and restoring HG-induced repression of CTGF expression by GDF11. Overall, the study shows that both natural and truncated GDF11s promote the healing process of skin wound in mice of both T1DM and T2DM partly via stimulating dermal fibrosis via the YAP—Smad2/3—CTGF pathway, suggesting it a potential agent for treating skin wound in diabetic population. •GDF11 has similar effect on the healing of diabetic wounds as the other three growth factors (PDGF, bFGF and EGF).•GDF11 can promote the expression of CTGF by promoting YAP and p-Smad2/3 forming a nuclear translocation complex.•The truncated GDF11 synthesized ourselves has a similar effect to the purchased one in promoting diabetic wound healing.•The truncated GDF11 might be considered a potential new agent for the treatment of diabetic wounds.