Claudin‐2 downregulation by KSHV infection is involved in the regulation of endothelial barrier function. (4th July 2014)

• Record Type: Journal Article
• Authors: Tan, Xiaohua; Li, Dongmei; Wang, Xiaobo; Zeng, Yan; Yan, Yutao; Yang, Lei
• Is Part Of: Journal of cutaneous pathology. Volume 41:Number 8(2014:Sep.)
• Page Start: 630
• Page End: 639
• Publication Date: 2014-07-04
• Subjects: Skin -- Diseases -- Periodicals; Dermatology -- Periodicals; 616
• DOI: 10.1111/cup.12332
• Languages: English
• ISSNs: 0303-6987

Abstract

<abstract abstract-type="main" id="cup12332-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cup12332-sec-0001" sec-type="section"> <title>Background</title> <p id="cup12332-para-0001">Kaposi sarcoma (KS), caused by the infection of Kaposi sarcoma‐associated herpesvirus (<italic>KSHV</italic>), 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.</p> </sec> <sec id="cup12332-sec-0002" sec-type="section"> <title>Methods</title> <p id="cup12332-para-0002">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.</p> </sec> <sec id="cup12332-sec-0003" sec-type="section"> <title>Results</title> <p id="cup12332-para-0003">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.</p> </sec> <sec id="cup12332-sec-0004" sec-type="section"> <title>Conclusion</title> <p id="cup12332-para-0004">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.</p> </sec> </abstract>