Xu Dan, Li Ting, Wang Ruikang, Mu Rong
Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China.
Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
Front Med (Lausanne). 2021 Jul 20;8:674523. doi: 10.3389/fmed.2021.674523. eCollection 2021.
Emerging evidence shows that integrin members are involved in inflammation and fibrosis in systemic sclerosis (SSc). This study aimed at evaluating the expression of integrin family genes in the skin tissue from SSc patients and exploring the potential pathogenic mechanism. We utilized the public datasets of SSc skin tissue from the Gene Expression Omnibus (GEO) database to analyze the expression and clinical significance of integrin family genes in SSc. The expression of integrin members in skin tissue was also assessed by immunohistochemistry. In addition, functional enrichment and pathway analysis were conducted. Compared with healthy controls, the mRNA and protein levels of , and were upregulated in the skin of SSc patients. Further analysis indicated that the mRNA expression levels of , and were positively correlated with modified Rodnan skin thickness score (mRSS). Functional enrichment and pathway analysis showed that integrin members may play multiple roles in the pathogenesis of SSc. Among them, , and might synergistically promote SSc through affecting extracellular matrix (ECM) turnover, ECM-receptor interaction, focal adhesion, and leukocyte trans-endothelial migration, while and also might affect angiogenesis and endothelial cell function. In addition, , and were associated with different pathways, respectively. was uniquely enriched for actin organization, while was for TGF-β signaling and for immune cell activation. Our results implied that the abnormal expression of integrin family genes including , and may participate in multiple pathological processes in SSc. Further investigations are required for confirming this speculation.
新出现的证据表明，整合素成员参与系统性硬化症（SSc）的炎症和纤维化过程。本研究旨在评估SSc患者皮肤组织中整合素家族基因的表达，并探索其潜在的致病机制。我们利用基因表达综合数据库（GEO）中SSc皮肤组织的公共数据集，分析整合素家族基因在SSc中的表达及临床意义。还通过免疫组织化学评估皮肤组织中整合素成员的表达。此外，进行了功能富集和通路分析。与健康对照相比，SSc患者皮肤中 、 和 的mRNA及蛋白水平上调。进一步分析表明， 、 和 的mRNA表达水平与改良Rodnan皮肤厚度评分（mRSS）呈正相关。功能富集和通路分析显示，整合素成员可能在SSc发病机制中发挥多种作用。其中， 、 和 可能通过影响细胞外基质（ECM）周转、ECM-受体相互作用、粘着斑和白细胞跨内皮迁移协同促进SSc，而 和 也可能影响血管生成和内皮细胞功能。此外， 、 和 分别与不同通路相关。 独特地富集于肌动蛋白组织， 富集于TGF-β信号通路， 富集于免疫细胞激活。我们的结果表明，包括 、 和 在内的整合素家族基因的异常表达可能参与SSc的多种病理过程。需要进一步研究来证实这一推测。
