Pleiotropic functions of pre-B-cell colony-enhancing factor (PBEF) revealed by transcriptomics of human pulmonary microvascular endothelial cells treated with PBEFsiRNA.

ABSTRACT

This study profiled transcriptomes of human pulmonary microvascular endothelial cells (HMVEC-L) treated with pre-B-cell colony-enhancing factor (PBEF) siRNA or scrambled RNA to gain insight into transcriptional regulations of PBEF on the endothelial function using the Affymetrix GeneChips HG-U133 plus 2. Several important themes are emerged from this study. First, PBEF affected expressions of multiple genes in the endothelium. Expression of 373 genes was increased and 64 genes decreased by at least 1.3-fold in the PBEFsiRNA-treated HMVEC-L versus the scramble RNA control. Second, the microarray results confirmed previous reports of PBEF-mediated gene expressions in some pathways but provided a more complete repertoire of molecules in those pathways. Third, most of the affected canonical pathways have not previously been reported to be PBEF responsive. Fourth, network analysis supports that PBEF has pleiotropic functions. Our first transcriptome analysis of human pulmonary microvascular endothelial cells treated with PBEFsiRNA has provided important insights into the transcriptional regulation of gene expression in HMVEC-L cells by PBEF. Further in-depth analysis of these transcriptional regulations may shed light on molecular mechanisms underlying PBEF-mediated endothelial functions and dysfunctions in various diseases and provide new leads of therapeutic targets to those diseases.