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MicroRNA-152-5p inhibits proliferation and migration and promotes apoptosis by regulating expression of Smad3 in human keloid fibroblasts
qianqian pang1, yuming wang1, mingyuan xu1, jiachao xu2, shengquan xu3, yichen shen1, jinghong Xu1,*, rui lei1
1Plastic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University,
2internal medicine, Haiyan Hospital of traditional Chinese medicine,
3Hand Surgery and Microsurgery Center, The First Affiliated Hospital, School of Medicine, Zhejiang University
Keloids are one of the most common pathological form of trauma healing, with features that seriously affect appearance and body function, are difficult to treat and have a high recurrence rate. 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 investigated 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 was significantly associated with the proliferation, migration and apoptosis of keloid cells. Overexpression of miR-152-5p significantly inhibited 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 Akt pathways and regulates collagen3 production. In summary, our study demonstrates that miR152-5p/Smad3 regulatory pathways involved in fibrotic progression may be a therapeutic target of keloids.
Abstract, Accepted Manuscript(in press) [Submitted on December 4, 2018, Accepted on January 5, 2019]
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