Role And Regulation Mechanism Of MicroRNA-152-5p In The Regulation Of Smad3-related Pathway In Human Keloid

Keloids are the most common pathological form of trauma healing,characterized by invasiveness beyond the original boundary of the insult and overproduction of extracellular matrix(ECM),as collagen by fibroblasts.However,the etiology and mechanism have yet to be discovered.Keloids seriously affect appearance and body function,which are difficult to treat and have a high recurrence rate after operation.Therefore,combined gene therapy has become a new research hotspot.And emerging evidence suggests that miRNAs are involved in a variety of pathological processes and play an important role in the process of fibrosis.In this study,we investigate the function and regulatory network of miR152-5p in keloids.The miRNA miR-152-5p is frequently downregulated in keloid tissue and primary cells compared to normal skin tissue and fibroblasts.In addition,the downregulation of miR-152-5p is significantly associated with the proliferation,migration,invasion and apoptosis rate of keloid cells.Overexpression of miR-152-5p significantly inhibites the progression of fibrosis in keloids.Upregulated Smad3 is a direct target of miR-152-5p,and knockdown of Smad3 also inhibits fibrosis progression,consistent with the overexpression of miR-152-5p.The interaction between miR-152-5p and Smad3 occurs through the Erk1/2 and Jak2/Stat3/Akt pathways and regulates collagen3 production.In summary,our study demonstrates that miR-152-5p/Smad3 regulatory pathways involved in fibrotic progression may be a potential therapeutic target of keloids.