title: Modulation of mesenchymal stem cells with miR-375 to improve their therapeutic outcome during scar formation.
abstract: Understanding of the mechanism of cutaneous scar formation with the goal of developing potential therapies to promote scar-less wound healing appears to be extremely critical. Mesenchymal stem cells (MSCs) have a demonstrate role in promoting scar-less wound healing. However, recent studies have shown that the function of MSCs may be attenuated due to insufficient activation in vivo. Here, we aimed to increase the activity and functions of MSCs to improve their effects during scar formation. We found that overexpression of microRNA-375 (miR-375) in MSCs significantly decreased the levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) protein, but not mRNA. Mechanistically, miR-375 inhibited TIMP-1 protein translation through binding to the 3'-UTR of the TIMP-1 mRNA in MSCs. Transplantation of miR-375-expressing MSCs significantly reduced the fibrosis in the scar region of the mice, possibly through reduction of reactive oxygen species (ROS), suppression of transition of myofibroblasts from fibroblasts, and increases in hepatic growth factor (HGF). Together, these data suggest that overexpression of miR-375 in MSCs may substantially improve the effects of MSCs on reduction of scar during wound healing. Our study sheds new light on a scar-less wound healing.
authors.affiliation: Wound Care Center, College of Life Sciences, Chinese PLA General Hospital Beijing 100853, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sheng
authors.affiliation: Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Zihao
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Oncology, Chinese PLA General Hospital Beijing 100853, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Song
authors.affiliation: Department of Dermatology, Affiliated Hospital of Hebei University of Engineering Handan 056029, China.
authors.forename: Heyong
authors.initials: H
authors.lastname: Niu
authors.affiliation: Department of Dermatology, Affiliated Hospital of Hebei University of Engineering Handan 056029, China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Miao
keywords: Scar formation; mesenchymal stem cells (MSCs); miR375; tissue inhibitor of metalloproteinases 1 (TIMP-1)