Let‑7f‑5p Regulated by Hsa_circ_0000437 Ameliorates Bleomycin‐Induced Skin Fibrosis

作者：Baiting Liu, Chenxi Li, Yunyao Bo, Guiping Tian, Lijun Yang, Jianjun Si, Lin Zhang, Yuan Yan · 发表于：Journal of Cellular Biochemistry · 年份：2024 · DOI：10.1002/jcb.30629 · 被引用次数：7 · 研究领域：Circular RNAs in diseases、Kruppel-like factors research、Cancer-related molecular mechanisms research

The current treatment of skin fibrosis is limited in its effectiveness due to a lack of understanding of the underlying mechanisms. Previous research has shown a connection between microRNAs (miRNAs) and the development of skin fibrosis. Therefore, investigating miRNA for the treatment of skin fibrotic diseases is highly important and merits further exploration. In this study, we have discovered that let-7f-5p could suppress the proliferation, migration, and expression of collagen type I alpha 1 (COL1A1) in human dermal fibroblasts (HDFs). It was further determined that let-7f-5p could target thrombospondin-1 (THBS1), thereby inhibiting the TGF-β2/Smad3 signaling pathway and exerting its biological effects. Additionally, let-7f-5p is regulated by Hsa_circ_0000437, which acts as a sponge molecule for let-7f-5p and consequently regulates the biological function of HDFs. Furthermore, our findings indicate that in vivo overexpression of let-7f-5p leads to a reduction in dermal thickness and COL1A1 expression, effectively inhibiting the progression of bleomycin (BLM)-induced skin fibrosis in mice. Hence, our research enhances the comprehension of the Hsa_circ_0000437/let-7f-5p/THBS1/TGF-β2/Smad3 regulatory network, highlighting the potential of let-7f-5p as a therapeutic approach for the treatment of skin fibrosis.