AUTHOR=Xu Dan , Li Ting , Wang Ruikang , Mu Rong 

TITLE=Expression and Pathogenic Analysis of Integrin Family Genes in Systemic Sclerosis

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.674523

DOI=10.3389/fmed.2021.674523

ISSN=2296-858X

ABSTRACT=<p><bold>Objectives:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> Compared with healthy controls, the mRNA and protein levels of <italic>ITGA5, ITGB2</italic>, and <italic>ITGB5</italic> were upregulated in the skin of SSc patients. Further analysis indicated that the mRNA expression levels of <italic>ITGA5, ITGB2</italic>, and <italic>ITGB5</italic> 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, <italic>ITGA5, ITGB2</italic>, and <italic>ITGB5</italic> might synergistically promote SSc through affecting extracellular matrix (ECM) turnover, ECM–receptor interaction, focal adhesion, and leukocyte trans-endothelial migration, while <italic>ITGA5</italic> and <italic>ITGB5</italic> also might affect angiogenesis and endothelial cell function. In addition, <italic>ITGA5, ITGB2</italic>, and <italic>ITGA5</italic> were associated with different pathways, respectively. <italic>ITGA5</italic> was uniquely enriched for actin organization, while <italic>ITGB5</italic> was for TGF-β signaling and <italic>ITGB2</italic> for immune cell activation.</p><p><bold>Conclusion:</bold> Our results implied that the abnormal expression of integrin family genes including <italic>ITGA5, ITGB2</italic>, and <italic>ITGB5</italic> may participate in multiple pathological processes in SSc. Further investigations are required for confirming this speculation.</p>