miR-3606-3p alleviates skin fibrosis by integratively suppressing the integrin/FAK, p-AKT/p-ERK, and TGF-β signaling cascades

作者：Y Chen, Yiyi Gong, Mengkun Shi, Haoxing Zhu, Yulong Tang, Delin Huang, Wei Wang, Chenyi Shi, Xueyi Xia, Ying Zhang, Jian-Lan Liu, Jia Huang, Mengguo Liu, Huyan Chen, Yanyun Ma, Ziyu Wang, Lei Wang, Wenzhen Tu, Yinhuan Zhao, Jinran Lin, Jin Li, Jörg H. W. Distler, Wenyu Wu, Jiucun Wang, Xiangguang Shi · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.11.027 · 被引用次数：17 · 研究领域：Dermatologic Treatments and Research、Systemic Sclerosis and Related Diseases、Hair Growth and Disorders

In Brief Current treatment options for systemic sclerosis (SSc) and keloid including surgery and corticosteroids each have their respective limitations, thus commanding the need for new methods of tackling these diseases. Impact: Our findings suggest that miR-3606-3p may be a novel potential target for various skin fibrosis diseases.Our findings add a new dimension to the interventional strategy for skin fibrosis by demonstrating the multiple effects of miR-3606-3p in simultaneously inhibiting fibroblast cell proliferation, inflammation, migration, and collagen deposition. Our study provides a valuable method to measure cell migration in vivo in a humanized keloid mouse model. • Downregulation of miR-3606-3p correlates with the disease severity of skin fibrosis. • miR-3606-3p targets the 3′-UTRs of ITGAV, GAB1 , and TGFBR2 in fibroblasts. • miR-3606-3p downregulation activates ITGAV/FAK, GAB1/AKT/ERK and TGFBR2/SMAD2/3. • These cascades integratively promote proliferation, migration, and inflammation. • miR-3606-3p alleviates skin fibrosis in keloid-bearing humanized mice. Fibroblast abnormalities are crucial causes of skin fibrosis, including systemic sclerosis (SSc) and keloids. However, their mechanisms, including underlying microRNA regulatory mechanisms, remain elusive. This study aimed to evaluate the roles, mechanisms, and therapeutic potential of miR-3606-3p in regulating multiple fibroblast abnormalities. The miR-3606-3p levels were evaluated in skin tissues and prim...