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Loss of Atg7 in Endothelial Cells Enhanced Cutaneous Wound Healing in a Mouse Model.
Li, Ke-Cheng; Wang, Chun-Hui; Zou, Jing-Jiang; Qu, Chen; Wang, Xing-Li; Tian, Xing-Song; Liu, Hong-Wei; Cui, Taixing.
Afiliación
  • Li KC; Department of Plastic Surgery,The First Affiliated Hospital of Jinan University,Guangzhou, Key Laboratory for Regenerative Medicine, Ministry of Education,Institute for New Technologies Plastic Surgery of Jinan University, Guangzhou, Guangdong, China.
  • Wang CH; Surgical Intensive Care Unit, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
  • Zou JJ; Department of Plastic Surgery,The First Affiliated Hospital of Jinan University,Guangzhou, Key Laboratory for Regenerative Medicine, Ministry of Education,Institute for New Technologies Plastic Surgery of Jinan University, Guangzhou, Guangdong, China.
  • Qu C; Ultrasound Diagnosis and Treatment Department, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China.
  • Wang XL; Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, Shandong, China.
  • Tian XS; Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
  • Liu HW; Department of Plastic Surgery,The First Affiliated Hospital of Jinan University,Guangzhou, Key Laboratory for Regenerative Medicine, Ministry of Education,Institute for New Technologies Plastic Surgery of Jinan University, Guangzhou, Guangdong, China. Electronic address: liuhongwei0521@hotmail.com.
  • Cui T; Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina. Electronic address: taixing.cui@uscmed.sc.edu.
J Surg Res ; 249: 145-155, 2020 05.
Article en En | MEDLINE | ID: mdl-31958599
BACKGROUND: Emerging evidence has linked autophagy to skin wound healing; however, the underlying cellular and molecular mechanisms remain poorly understood. The present study was designed to determine the role of autophagy in endothelial cell (EC)-mediated skin wound healing in mice. METHODS: Autophagy-related gene (Atg7) in mouse ECs was inactivated by the Cre-loxP system under the control of an EC-specific VE-Cadherin (Cdh5) promoter (Atg7EC-/- mice). Full-thickness skin wounds were created on the dorsum of wild-type (WT), Cdh5-Cre+, floxed Atg7 (Atg7F/F), and Atg7EC-/- mice. Autophagic activity was determined by autophagic flux assay in the primary culture of ECs isolated from these mice. The wound re-epithelialization and angiogenesis was examined by histological analyses. The angiogenic activity of ECs was evaluated by tube formation assay in vitro. EC proliferation was examined by a cell count CCK-8 kit. EC-originated intercellular communication with dermal fibroblasts and keratinocytes was assessed by measuring the effect of EC conditional medium on the growth of keratinocytes and fibroblasts. The levels of VEGF, EGF, bFGF in EC conditional medium were measured by ELISA. RESULTS: Autophagy deficiency in ECs markedly enhanced the re-epithelialization and the wound closure during skin wound healing. However, it has minimal impact on angiogenesis in the wounded skin. Notably, autophagy deficiency in ECs did not affect their proliferation and migration or angiogenic activity per se but enhanced the EC conditional medium-induced proliferation and migration of keratinocytes and fibroblasts. CONCLUSIONS: These results demonstrate for the first time an inhibitory role of autophagy in the EC-originated paracrine regulation of skin wound healing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Cicatrización de Heridas / Células Endoteliales / Herida Quirúrgica / Proteína 7 Relacionada con la Autofagia Límite: Animals / Female / Humans / Male Idioma: En Revista: J Surg Res Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Cicatrización de Heridas / Células Endoteliales / Herida Quirúrgica / Proteína 7 Relacionada con la Autofagia Límite: Animals / Female / Humans / Male Idioma: En Revista: J Surg Res Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos