title: Claudin-2 downregulation by KSHV infection is involved in the regulation of endothelial barrier function.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Tan
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Yutao
authors.initials: Y
authors.lastname: Yan
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
mesh_terms: D015153:Blotting, Western; D002199:Capillary Permeability / Q000235:genetics*; D057167:Claudins / Q000096:biosynthesis*; D016000:Cluster Analysis; D060085:Coinfection; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D015658:HIV Infections / Q000150:complications; D019288:Herpesvirus 8, Human; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000150:complications / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome
chemical_list: C491875:CLDN2 protein, human; D057167:Claudins
keywords: Kaposi sarcoma; Kaposi sarcoma-associated herpes virus (KSHV); barrier function; claudin-2