Department of Otolaryngology-Head and Neck Surgery, The First Afiliated Hospital of Xiamen University, Xiamen, China.
Physiol Res. 2022 Apr 30;71(2):285-295. doi: 10.33549/physiolres.934804. Epub 2022 Apr 11.
Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles due to multiple etiologies. Emilin 1 plays a determinant role in fibers formation, but its role in the progression of GMC remains unclear. The present study was aimed to search for the predictive role and regulatory mechanism of Emilin 1 on GMC. Here, Protein and mRNA expression of Emilin 1 were decreased in GMC tissues compared to normal muscle tissues. Using the anslysis of target prediction, Emilin 1 was observed to be a potential downstream sponge of miR-491-5p. In comparison to Emilin 1, miR-491-5p showed a aberrant elevation in GMC tissues, which was further proven to have a negative correlation with Emilin 1. The direct binding of miR-491-5p to Emilin 1 mRNA was confirmed by luciferase reporter gene assay, and miR-491-5p mimics inhibited, while miR-491-5p inhibitor promoted the protein expression and secretion of Emilin 1 in contraction bands (CB) fibroblasts. Additionally, miR-491-5p mimics promoted the expression of cyclin-dependent kinase 2 and cyclin D1 and the proliferation of CB fibroblasts, which could be reversed by Emilin 1 overexpression. Mechanistically, miR-491-5p mimics possibly activated transforming growth factor beta1 (TGF-beta1)/Smad3 signal cascade via binding to 3'-untranslated region of Emilin 1 mRNA, thereby promoting the progression of fibrosis of CB fibroblasts. Collectively, miR-491-5p inhibited Emilin 1 expression, and subsequently promoted CB fibroblasts proliferation and fibrosis via activating TGF-beta1/Smad3 signal axis. MiR-491-5p might be a potentially effective biomarker for predicting GMC, providing a novel therapeutic strategy for GMC.
臀肌挛缩症（GMC）是一种由多种病因引起的臀肌慢性纤维性疾病。弹力蛋白 1 在纤维形成中起决定作用，但它在 GMC 进展中的作用尚不清楚。本研究旨在探讨弹力蛋白 1 在 GMC 中的预测作用和调控机制。研究发现，与正常肌肉组织相比，GMC 组织中的弹力蛋白 1 蛋白和 mRNA 表达降低。通过靶基因预测分析，发现弹力蛋白 1 是 miR-491-5p 的潜在下游海绵。与弹力蛋白 1 相比，miR-491-5p 在 GMC 组织中异常升高，进一步证明其与弹力蛋白 1 呈负相关。荧光素酶报告基因实验证实 miR-491-5p 可直接结合弹力蛋白 1 mRNA。miR-491-5p 模拟物抑制，而 miR-491-5p 抑制剂促进收缩带（CB）成纤维细胞中弹力蛋白 1 的蛋白表达和分泌。此外，miR-491-5p 模拟物促进 CB 成纤维细胞中细胞周期蛋白依赖性激酶 2 和细胞周期蛋白 D1 的表达和增殖，而弹力蛋白 1 的过表达可逆转这一过程。机制上，miR-491-5p 模拟物可能通过结合弹力蛋白 1 mRNA 的 3'-非翻译区，激活转化生长因子β1（TGF-β1）/Smad3 信号级联，从而促进 CB 成纤维细胞的纤维化进程。总之，miR-491-5p 抑制弹力蛋白 1 的表达，进而通过激活 TGF-β1/Smad3 信号轴促进 CB 成纤维细胞增殖和纤维化。miR-491-5p 可能是预测 GMC 的潜在有效生物标志物，为 GMC 提供了新的治疗策略。
