HGF accelerates wound healing by promoting the dedifferentiation of epidermal cells through β1-integrin/ILK pathway.
Skin wound healing is a critical and complex biological process after trauma. This process is activated by signaling pathways of both epithelial and nonepithelial cells, which release a myriad of different cytokines and growth factors. Hepatocyte growth factor (HGF) is a cytokine known to play multiple roles during the various stages of wound healing. This study evaluated the benefits of HGF on reepithelialization during wound healing and investigated its mechanisms of action. Gross and histological results showed that HGF significantly accelerated reepithelialization in diabetic (DB) rats. HGF increased the expressions of the cell adhesion molecules β1-integrin and the cytoskeleton remodeling protein integrin-linked kinase (ILK) in epidermal cells in vivo and in vitro. Silencing of ILK gene expression by RNA interference reduced expression of β1-integrin, ILK, and c-met in epidermal cells, concomitantly decreasing the proliferation and migration ability of epidermal cells. β1-Integrin can be an important maker of poorly differentiated epidermal cells. Therefore, these data demonstrate that epidermal cells become poorly differentiated state and regained some characteristics of epidermal stem cells under the role of HGF after wound. Taken together, the results provide evidence that HGF can accelerate reepithelialization in skin wound healing by dedifferentiation of epidermal cells in a manner related to the β1-integrin/ILK pathway.
The Neurology Department of the 148th Hospital, 20 Zhanbei Road, Zibo 255300, China.
Jin-Feng
JF
Li
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
Hai-Feng
HF
Duan
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
Chu-Tse
CT
Wu
Medical Research Center of Naval General Hospital, 6 Fucheng Road, Beijing 10037, China.
Da-Jin
DJ
Zhang
Wuhan University of Science and Technology, Wuhan, Hubei 430081, China.
Youping
Y
Deng
The Neurology Department of the 148th Hospital, 20 Zhanbei Road, Zibo 255300, China.
Hong-Lei
HL
Yin
The Neurology Department of the 148th Hospital, 20 Zhanbei Road, Zibo 255300, China.
Bing
B
Han
The Neurology Department of the 148th Hospital, 20 Zhanbei Road, Zibo 255300, China.
Hui-Cui
HC
Gong
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Hong-Wei
HW
Wang
The Neurology Department of the 148th Hospital, 20 Zhanbei Road, Zibo 255300, China.
Yun-Liang
YL
Wang
D000818:Animals; D054337:Cell Dedifferentiation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy; D004847:Epithelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000378:metabolism*; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*; D000099200:Scaffold Protein ILK
D017228:Hepatocyte Growth Factor; D019012:Integrin beta1; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK