Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 193 (3), 299-318

Targets of Transcriptional Regulation by Two Distinct Type I Receptors for Transforming Growth Factor-Beta in Human Umbilical Vein Endothelial Cells

Affiliations

Targets of Transcriptional Regulation by Two Distinct Type I Receptors for Transforming Growth Factor-Beta in Human Umbilical Vein Endothelial Cells

Tatsuru Ota et al. J Cell Physiol.

Abstract

Transforming growth factor-beta (TGF-beta) plays a crucial role in vascular development and homeostasis by regulating many transcriptional targets. Activin receptor-like kinase 5 (ALK-5) is a TGF-beta type I receptor expressed in various TGF-beta-responsive cells. In contrast, ALK-1 functions as a TGF-beta type I receptor in endothelial cells, and is responsible for human hereditary hemorrhagic telangiectasia (HHT) type II. ALK-5 and ALK-1 mediate TGF-beta signals through distinct Smad proteins, i.e., Smad2/Smad3 and Smad1/Smad5, respectively. To identify target genes of ALK-1 and ALK-5 in endothelial cells, we conducted oligonucleotide microarray analysis. Human umbilical vein endothelial cells (HUVEC) were infected with recombinant adenoviruses carrying a constitutively active form of ALK-1 or ALK-5. ALK-5 inhibited the proliferation, network formation, and tube formation of HUVEC and induced their apoptosis, whereas ALK-1 did not exhibit significant effects on HUVEC in vitro. mRNAs were extracted from HUVEC and used for hybridization of oligonucleotide arrays representing approximately 7,000 human genes. Northern blot and quantitative real-time polymerase chain reaction (PCR) analyses were also performed for some of these genes, confirming the validity of this microarray analysis. We found that ALK-1 specifically upregulated Smad6, Smad7, Id1, Id2, endoglin, STAT1, and interleukin 1 receptor-like 1. ALK-5, in contrast, upregulated PlGF, SM22alpha, connexin 37, betaIG-H3, and LTBP1. ALK-1 downregulated Smad1, CXCR4, Ephrin-A1, and plakoglobin, whereas ALK-5 downregulated claudin 5 and integrin beta(5). These results revealed some new targets of TGF-beta in endothelial cells, and differences in transcriptional regulation patterns between ALK-1 and ALK-5.

Similar articles

See all similar articles

Cited by 56 articles

See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources

Feedback