MAPK/AP-1 signaling pathway is involved in the protection mechanism of bone marrow mesenchymal stem cells-derived exosomes against Ultraviolet-induced photoaging in human dermal fibroblasts

作者：Yan, Tingting^*; Huang, Lining; Yan, Yunling; Zhong, Yiping; Xie, Heng; Wang, Xiaohua

来源：Skin Pharmacology and Physiology, 2023, 36(2): 98-105.

DOI：10.1159/000529551

Introduction: The role of bone marrow mesenchymal stem cells derived exosomes (BMSCs-exo) in skin photoaging was explored in human dermal fibroblasts (HDFs). The underlying mechanism was further explored.Methods: HDFs were exposed to UVB irradiation to establish the cell photodamage models. The cell viability, and levels of oxidative stress-related factors were tested. ELISA was done to detect TNF-alpha, IL-6 and IL-1 beta concentration. Western blot was applied for protein examination.Results: UVB treatment led to the inhibition of cell viability. But after BMSCs-exo addition, the inhibitory effect was returned in a dose manner. UVB exposure contributed to the increase of ROS and LDH, and the downregulation of SOD. In addition, excessive secretion of TNF-alpha, IL-6 and IL-1 beta was also detected in cells exposed to UVB. However, BMSCs-exo addition eliminated the effects of UVB on oxidative stress and inflammation in HDFs. BMSCs-exo inhibited MMP-1 and MMP-3 expression, but promoted collagen I expression. UVB radiation activated the MAPK/AP-1 signaling, manifested as the increase of p-p38, c-Jun and c-Fos protein levels, which was reversed by BMSCs-exo. As a p38 agonist, anisomycin (ANS) counteracted the effect of BMSCs-exo on HDFs viability, oxidative stress and inflammation.Conclusion: BMSCs-exo protected HDFs against UVB-induced inhibition of cell viability and the activation of cell oxidative stress and inflammation, which might be related to the inhibition of the MAPK/AP-1 signaling pathway.

• 单位
  南方医科大学