Distinct regulation of gene expression in human endothelial cells by TGF-beta and its receptors.
Transforming growth factor beta (TGF-beta) and its signaling mediators play essential roles in angiogenesis-formation of new blood vessels, as evidenced by targeted gene disruption in mice and their mutations in human vascular dysplasia. However, little is known about the molecular basis of TGF-beta function in vascular formation. To study the function of TGF-beta signaling in angiogenesis and to elucidate the signaling specificity of TGF-beta receptors at the gene transcriptional level, we analyzed the expression profile of the genes regulated by TGF-beta and its type I receptors ALK1 and ALK5 in human microvessel endothelial cells (ECs). Global change of gene expression profiles was examined by microarray and RT-PCR analyses in the ECs treated with TGF-beta1 or by adenoviral expression of the active ALK1 or ALK5. We found that the profiles of the genes regulated by TGF-beta, ALK1 and ALK5 are distinct from each other, although some of genes are modulated by all of them. TGF-beta regulated far more genes than ALK1 and ALK5 did. ALK1 enhanced the formation of tube-like structures of ECs, while ALK5 stimulates EC aggregation. Our results suggest that ALK1 appears to have important functions in regulating proliferation of ECs, whereas ALK5 tends to modulate cell-cell interaction and cell adhesion and extracellular matrix remodeling.
Wu
Xiaoping
X
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Ma
Jing
J
Han
Jing-Dong
JD
Wang
Nanping
N
Chen
Ye-Guang
YG
D030201:Activin Receptors, Type I / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D046228:Microarray Analysis; D018919:Neovascularization, Physiologic; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse