Transcriptional profiling of human cavernosal endothelial cells reveals distinctive cell adhesion phenotype and role for claudin 11 in vascular barrier function.
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.
Wessells
Hunter
H
Departments of Urology, Harborview Medical Center, 325 Ninth Ave., Seattle Washington 98104, USA. wessells@u.washington.edu
Sullivan
Chris J
CJ
Tsubota
Yoshiaki
Y
Engel
Karen L
KL
Kim
Bryan
B
Olson
N Eric
NE
Thorner
Daniel
D
Chitaley
Kanchan
K
D000368:Aged; D002426:Cavernous Sinus; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D062507:Claudin-5; D057167:Claudins; D016000:Cluster Analysis; D017097:Electric Impedance; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010413:Penis / Q000098:blood supply* / Q000166:cytology*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
C120453:CLDN11 protein, human; C107466:CLDN5 protein, human; D062507:Claudin-5; D057167:Claudins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering