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微小 RNA-152-5p 通过调控人瘢痕疙瘩成纤维细胞中 Smad3 的表达抑制增殖、迁移并促进凋亡。

MicroRNA-152-5p inhibits proliferation and migration and promotes apoptosis by regulating expression of Smad3 in human keloid fibroblasts.

机构信息

Department of Plastic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.

Department of Internal Medicine, Haiyan Hospital of Traditional Chinese Medicine, Jiaxin 314300, China.

出版信息

BMB Rep. 2019 Mar;52(3):202-207. doi: 10.5483/BMBRep.2019.52.3.278.

Abstract

Keloids are 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 miR-152-5p 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 and apoptosis of keloid cells. Overexpression of miR-152-5p significantly inhibits the progression of fibrosis in keloids. 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 miR-152-5p/Smad3 regulatory pathways involved in fibrotic progression may be a potential therapeutic target of keloids. [BMB Reports 2019; 52(3): 202-207].

摘要

瘢痕疙瘩是创伤愈合最常见的病理性形式,其特征严重影响外观和身体功能,治疗困难且复发率高。新出现的证据表明,miRNA 参与多种病理过程,并在纤维化过程中发挥重要作用。在这项研究中,我们研究了 miR-152-5p 在瘢痕疙瘩中的功能和调控网络。与正常皮肤组织和成纤维细胞相比,miR-152-5p 在瘢痕疙瘩组织和原代细胞中经常下调。此外,miR-152-5p 的下调与瘢痕疙瘩细胞的增殖、迁移和凋亡显著相关。miR-152-5p 的过表达可显著抑制瘢痕疙瘩中的纤维化进展。Smad3 是 miR-152-5p 的直接靶标,Smad3 的敲低也抑制纤维化进展,与 miR-152-5p 的过表达一致。miR-152-5p 和 Smad3 之间的相互作用通过 Erk1/2 和 Akt 途径发生,并调节胶原 3 的产生。总之,我们的研究表明,miR-152-5p/Smad3 调节通路参与纤维化进展,可能是瘢痕疙瘩的潜在治疗靶点。[BMB 报告 2019;52(3):202-207]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b07/6476487/468ecddda343/bmb-52-202f1.jpg

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