RRC ID 58403
著者 Li KC, Wang CH, Zou JJ, Qu C, Wang XL, Tian XS, Liu HW, Cui T.
タイトル Loss of Atg7 in Endothelial Cells Enhanced Cutaneous Wound Healing in a Mouse Model.
ジャーナル J Surg Res
Abstract 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.
巻・号 249
ページ 145-155
公開日 2020-5-1
DOI 10.1016/j.jss.2019.12.004
PII S0022-4804(19)30830-3
PMID 31958599
MeSH Animals Autophagy / genetics* Autophagy / immunology Autophagy-Related Protein 7 / genetics* Cell Communication / genetics Cell Communication / immunology Cell Movement / genetics Cell Proliferation / genetics Cells, Cultured Culture Media, Conditioned / metabolism Disease Models, Animal Endothelial Cells / immunology* Endothelium, Vascular / cytology Female Fibroblasts Humans Keratinocytes Male Mice Mice, Knockout Myocardium / cytology Neovascularization, Physiologic / genetics Neovascularization, Physiologic / immunology Paracrine Communication / genetics Paracrine Communication / immunology Primary Cell Culture Skin / blood supply Skin / injuries Surgical Wound / immunology* Wound Healing / immunology*
IF 1.872
引用数 1
リソース情報
実験動物マウス RBRC02759