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Physiol. Genomics 39: 100-108, 2009. First published July 21, 2009; doi:10.1152/physiolgenomics.90354.2008
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Received 23 July 2008; accepted in final form 16 July 2009.
Physiological Genomics 39:100-108 (2009)
Copyright © 2009 the American Physiological Society © 2009 American Physiological Society

Call for Papers: Comparative Genomics

Transcriptional profiling of human cavernosal endothelial cells reveals distinctive cell adhesion phenotype and role for claudin 11 in vascular barrier function

Hunter Wessells 1,3, Chris J. Sullivan 5, Yoshiaki Tsubota 2,3, Karen L. Engel 1,2, Bryan Kim 1, N. Eric Olson 4, Daniel Thorner 1 and Kanchan Chitaley 1

Departments of 1Urology and
2Pathology, University of Washington School of Medicine;
3Harborview Medical Center and
4Geospiza Incorporated, Seattle, Washington; and
5Department of Biological Sciences, California State University, Sacramento, California

To determine specific molecular features of endothelial cells (ECs) relevant to the physiological process of penile erection we compared gene expression of human EC derived from corpus cavernosum of men with and without erectile dysfunction (HCCEC) to coronary artery (HCAEC) and umbilical vein (HUVEC) using Affymetrix GeneChip microarrays and GeneSifter software. Genes differentially expressed across samples were partitioned around medoids to identify genes with highest expression in HCCEC. A total of 190 genes/transcripts were highly expressed only in HCCEC. Gene Ontology classification indicated cavernosal enrichment in genes related to cell adhesion, extracellular matrix, pattern specification and organogenesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed high expression of genes relating to ECM-receptor interaction, focal adhesions, and cytokine-cytokine receptor interaction. Real-time PCR confirmed expression differences in cadherins 2 and 11, claudin 11 (CLDN11), desmoplakin, and versican. CLDN11, a component of tight junctions not previously described in ECs, was highly expressed only in HCCEC and its knockdown by siRNA significantly reduced transendothelial electrical resistance in HCCEC. Overall, cavernosal ECs exhibited a transcriptional profile encoding matrix and adhesion proteins that regulate structural and functional characteristics of blood vessels. Contribution of the tight junction protein CLDN11 to barrier function in endothelial cells is novel and may reflect hemodynamic requirements of the corpus cavernosum.

penis; tight junctions; microarray; gene ontology






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