人脐带MSC外泌体介导WNT4信号通路，参与皮肤创伤修复

niceman1987 · 发表于 2015-4-29 17:52:23

　　Mesenchymal stem cell‐derived exosomes （MSC‐Ex） play important roles intissue injury repair, however, the roles of MSC‐Ex in skin damage repairand its mechanisms are largely unknown. Herein, we examined the benefitof human umbilical cord mesenchymal stem cell derived exosome（hucMSC‐Ex） in cutaneous wound healing using a rat skin burn model. Wefound that hucMSC‐Ex‐treated wounds exhibited significantly acceleratedre‐epithelialization, with increased expression of CK19, PCNA, collagen I（compared to collagen III） in vivo. HucMSC‐Ex promoted proliferation andinhibited apoptosis of skin cells after heat‐stress in vitro. We also discoveredthat Wnt4 was contained in hucMSC‐Ex, and hucMSC‐Ex derived Wnt4promoted β‐catenin nuclear translocation and activity to enhance proliferationand migration of skin cells, which could be reversed by β‐catenin inhibitorICG001. In vivo studies confirmed that the activation of Wnt/β‐catenin by hucMSC‐Ex played a key role in wound re‐epithelialization andcell proliferation. Furthermore, knockdown of Wnt4 in hucMSC‐Ex abrogatedβ‐catenin activation and skin cell proliferation and migration in vitro. The in vivo therapeutic effects were also inhibited when the expression ofWnt4 in hucMSC‐Ex was interfered. In addition, the activation of AKTpathway by hucMSC‐Ex was associated with the reduction of heat stressinducedapoptosis in rat skin burn model. Collectively, our findings indicatethat exosome‐delivered Wnt4 provides new aspects for the therapeuticstrategy of MSCs in cutaneous wound healing.