Hypoxic ucMSC-secreted exosomal miR-125b promotes endothelial cell survival and migration during wound healing by targeting TP53INP1

Molecular Therapy: Nucleic Acids

Xiao-Fei Zhang¹  Kun-Peng Huang²  Hong-Ji Zhang²  Zi-Xuan Wang²  Jin-Xiang Zhang²  Yun-Wei Zhang³  Guo-Liang Wang⁴  Zi-Han Chen⁵  Chang-Yan Wang⁵  Hui Wang⁵  Ting Wang⁵ 

[1] Center for Translational Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;Department of Emergency, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;Department of Medical Genetics, Basic school of Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China;

关键词: skin wound repair;    hypoxia;    ucMSCs;    exosomes;    microRNA-125b;    TP53INP1;   

DOI  :  

来源: DOAJ

【 摘 要 】

A hypoxic microenvironment is a common feature of skin wounds. Our previous study demonstrated that three-dimensional coculture of umbilical cord-derived mesenchymal stem cells (ucMSCs) and endothelial cells facilitates cell communication and host integration in skin tissue engineering. Here, we aimed to identify the mechanism by which ucMSCs affect endothelial cells under hypoxic conditions after skin injury. We demonstrate that hypoxia enhances the exosome-mediated paracrine function of ucMSCs, which increases endothelial cell proliferation and migration. In a mouse full-thickness skin injury model, ucMSC-derived exosomes can be taken up by endothelial cells and accelerate wound healing. Hypoxic exosomes lead to a better outcome than normoxic exosomes by promoting proliferation and inhibiting apoptosis. Mechanistically, microRNA-125b (miR-125b) transcription is induced by hypoxia in ucMSCs. After being packaged into hypoxic exosomes and transported to endothelial cells, miR-125b targets and suppresses the expression of tumor protein p53 inducible nuclear protein 1 (TP53INP1) and alleviates hypoxia-induced cell apoptosis. Inhibition of miR-125b-TP53INP1 interaction attenuates the protective effect of hypoxic exosomes. Moreover, artificial agomiR-125b can accelerate wound healing in vivo. Our findings reveal communication between ucMSCs and endothelial cells via exosomal miR-125b/TP53INP1 signaling in the hypoxic microenvironment and present hypoxic exosomes as a promising therapeutic strategy to enhance cutaneous repair.

【 授权许可】

Unknown