2. Academic Validation
  3. Dedicator of Cytokinesis 5 Regulates Keratinocyte Function and Promotes Diabetic Wound Healing

Dedicator of Cytokinesis 5 Regulates Keratinocyte Function and Promotes Diabetic Wound Healing

  • Diabetes. 2021 May;70(5):1170-1184. doi: 10.2337/db20-1008.
Hua Qu 1,  Tian Miao 1 2,  Yuren Wang 1,  Liang Tan 3 4,  Bangliang Huang 1,  Linlin Zhang 1,  Xiufei Liu 1,  Min Long 1,  Rui Zhang 1,  Xiaoyu Liao 1,  Xiaoli Gong 1,  Ju Wang 3,  Xin Xiong 1,  Junli Liu 5,  Xi Li 6,  Jiang Yu 7,  Gangyi Yang 8,  Zhiming Zhu 9,  Hongting Zheng 10,  Yi Zheng 10
Affiliations

Affiliations

  • 1 Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Department of Endocrinology, Second Affiliated Hospital of Army Medical University, Chongqing, China.
  • 2 Department of Respiratory and Critical Care Medicine, General Hospital of Western Theater Command, Chengdu, China.
  • 3 Department of Neurosurgery, Southwest Hospital, Army Medical University, Chongqing, China.
  • 4 Department of Electrical and Computer Engineering, Faculty of Science and Technology, University of Macau, Macau, China.
  • 5 Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 Biology Science Institutes, Chongqing Medical University, Chongqing, China.
  • 7 Department of Outpatient, Second Affiliated Hospital of Army Medical University, Chongqing, China.
  • 8 Department of Endocrinology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 9 Department of Hypertension and Endocrinology, Third Affiliated Hospital of Army Medical University, Chongqing, China.
  • 10 Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Department of Endocrinology, Second Affiliated Hospital of Army Medical University, Chongqing, China cecilia.zy@163.com fnf7703@hotmail.com.
PMID: 33627322 DOI: 10.2337/db20-1008
Abstract

Cutaneous wound healing is a fundamental biologic and coordinated process, and failure to maintain this process contributes to the dysfunction of tissue homeostasis, increasing the global burden of diabetic foot ulcerations. However, the factors that mediate this process are not fully understood. Here, we identify the pivotal role of dedicator of cytokinesis 5 (Dock5) in keratinocyte functions contributing to the process of skin wound healing. Specifically, Dock5 is highly upregulated during the proliferative phase of wound repair and is predominantly expressed in epidermal keratinocytes. It regulates keratinocyte adhesion, migration, and proliferation and influences the functions of extracellular matrix (ECM) deposition by facilitating the ubiquitination of transcription factor ZEB1 to activate laminin-332/Integrin signaling. Genetic ablation of Dock5 in mice leads to attenuated reepithelialization and granulation tissue formation, and Dock5 overexpression-improved skin repair can be abrogated by LAMA3 knockdown. Importantly, Dock5 expression in the skin edge is reduced in patients and animal models of diabetes, further suggesting a direct correlation between its abundance and healing capability. The rescue of Dock5 expression in diabetic mice causes a significant improvement in reepithelialization, collagen deposition, ECM production, and granulation. Our study provides a potential therapeutic target for wound healing impairment during diabetes.

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