Zheng Wei, Chen Chen, Chen Shuai, Fan Cunyi, Ruan Hongjiang
Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
Department of Arthroscopic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
J Adv Res. 2018 Aug 30;15:49-58. doi: 10.1016/j.jare.2018.08.001. eCollection 2019 Jan.
The dysregulation of long non-coding RNAs (lncRNAs) is associated with the development of various diseases. However, little is known about the regulatory function of lncRNAs in peritendinous fibrosis. Therefore, the expression profiles of lncRNAs and mRNAs in normal tendon and fibrotic peritendinous tissues were analyzed in this study using RNA sequencing. In total, 219 lncRNAs and 3403 mRNAs were identified that were differentially expressed between the two sets of tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the dysregulated mRNAs were mainly associated with immune regulation, inflammation, extracellular matrix (ECM) production and remodeling, and cell cycle regulation. An lncRNA-mRNA co-expression network revealed 181 network pairs comprising eight dysregulated lncRNAs and 146 mRNAs. The results of the bioinformatics analysis indicated that the dysregulated lncRNAs play a role in fibrogenesis through regulation of the cell cycle, inflammation, and ECM production. Furthermore, silencing the lncRNA dnm3os prevented transforming growth factor (TGF)-β1-induced tenocyte proliferation and expression of genes related to fibrogenesis. These findings provide a basis for investigations into the regulatory mechanisms underlying the development and progression of peritendinous fibrosis.
长链非编码RNA(lncRNAs)的失调与多种疾病的发生发展相关。然而,关于lncRNAs在腱周纤维化中的调控功能知之甚少。因此,本研究采用RNA测序分析了正常肌腱和纤维化腱周组织中lncRNAs和mRNAs的表达谱。共鉴定出219个lncRNAs和3403个mRNAs在两组组织之间存在差异表达。基因本体论和京都基因与基因组百科全书通路分析显示,失调的mRNAs主要与免疫调节、炎症、细胞外基质(ECM)产生和重塑以及细胞周期调控有关。一个lncRNA-mRNA共表达网络显示了181个网络对,包括8个失调的lncRNAs和146个mRNAs。生物信息学分析结果表明,失调的lncRNAs通过调节细胞周期、炎症和ECM产生在纤维生成中发挥作用。此外,沉默lncRNA dnm3os可阻止转化生长因子(TGF)-β1诱导腱细胞增殖及与纤维生成相关基因的表达。这些发现为研究腱周纤维化发生发展的调控机制提供了依据。