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Claudin‐2 downregulation by KSHV infection is involved in the regulation of endothelial barrier function
Author(s) -
Tan Xiaohua,
Li Dongmei,
Wang Xiaobo,
Zeng Yan,
Yan Yutao,
Yang Lei
Publication year - 2014
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.12332
Subject(s) - claudin , gene knockdown , tight junction , downregulation and upregulation , barrier function , biology , microarray , cancer research , microarray analysis techniques , sarcoma , gene , gene expression , immunology , pathology , medicine , microbiology and biotechnology , genetics
Background Kaposi sarcoma ( KS ), caused by the infection of Kaposi sarcoma‐associated herpesvirus ( KSHV ), is a disease manifested mainly by dark purple skin and mouth nodules. Cancer care studies showed that co‐infection of KSHV and human immunodeficiency virus ( HIV ) was able to increase the patients' survival, but the underlying mechanisms are still elusive. Methods To understand the mechanism underlying the prolonged survival in KSHV‐HIV co‐infected patients, we performed microarray analysis on RNA extracted from biopsies from KS tumors and adjacent healthy tissues in four KS patients. Subsequently, we performed hierarchical clustering, gene ontology (GO) and ingenuity pathway analysis. We then characterized the roles of tight junction protein claudin‐2 in the endothelial barrier function. Results Three hundred and forty‐three differentially expressed genes were identified, of which 246 genes exhibited significantly increased expression in the tumor compared to the adjacent healthy tissue and 97 genes showed downregulated expression, including claudin‐2. Knockdown of claudin‐2 in cultured endothelial cells enhances barrier function by altering the charge selectivity, but not the size selectivity. Conclusion Claudin‐2 expression is decreased in KS tumors from patients co‐infected with KSHV and HIV . Decreased claudin‐2 enhances endothelial barrier function and may play a role in the prolonged survival of patients with KSHV and HIV co‐infection.