Department of Biology , University of Houston , TX 77204-5513 .
Mech Dev 44 : 33-40 ( 1993)
Abstract
Development and LpS1 transcription in Lytechinus embryos are arrested at the mesenchyme blastula stage when collagen deposition is inhibited by the lathrytic agent beta-aminopropionitrile ( BAPN ) or by proline analogs .
We found that human recombinant platelet derived growth factor-BB ( PDGF-BB ) and transforming growth factor-alpha ( TGF-alpha ) synergistically rescue collagen disrupted/developmentally arrested L. pictus and L. variegatus embryos so that development and RNA accumulation of LpS1 proceed .
In addition , nonspecific antagonists of PDGF block gastrulation and LpS1 RNA accumulation .
The embryos recover and LpS1 RNA accumulation resumes when the antagonists are removed .
These data suggest that a growth factor mediated pathway , associated with the ECM , is required for sea urchin gastrulation , spiculogenesis , and LpS1 gene activation .
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Department of Cardiovascular Biochemistry , Bristol-Myers Squibb Pharmaceutical Research Institute , Princeton , New Jersey 08543 .
J Clin Invest 93 : 788-98 ( 1994)
Abstract
By means of a rat aortic smooth muscle ( RASM ) cell culture model , the effects of angiotensin II ( AII ) on early proto-oncogene gene expression , DNA synthesis , and cell proliferation were measured and compared to known mitogens .
In 24-h [ 3H]-thymidine incorporation assays , AII was found to be a weak mitogen when compared to potent mitogens such as fetal bovine serum and platelet-derived growth factor ( PDGF ) .
In contrast , when assays were carried out for 48 h , AII induced a significant dose-dependent stimulation of DNA synthesis , which more than doubled at 3 nM AII , and was maximal ( five- to eightfold above control ) at 100 nM AII .
Treatment of cells with the AII type 1 receptor antagonist losartan inhibited the mitogenic effects of AII .
AII also stimulated smooth muscle cell proliferation , as indicated by an absolute increase in cell number after AII stimulation of RASM cells for 5 d . AII stimulation of RASM cell growth correlated with the increased expression of specific endogenous growth factors , including transforming growth factor beta 1 ( TGF-beta 1 ) and PDGF A-chain .
However , addition of either PDGF- or TGF-beta 1-neutralizing antibodies failed to significantly reduce the delayed mitogenic effects induced by AII .
In contrast , we found that AII-stimulated mitogenesis could be inhibited in a dose-dependent manner by the growth factor inhibitor drug suramin .
Taken together , our results indicate that enhanced endogenous growth factor expression may represent the direct mechanism by which AII promotes smooth muscle cell growth in some vascular hyperproliferative diseases .