Molecular Cloning ofa Diverged HomeoboxGeneThatIs Rapidly Down-Regulated during theGJ/G1 Transition inVascular SmoothMuscleCells

Adultvascular smoothmuscle cells dedifferentiate andreenter thecell cycle inresponsetogrowthfactor stimulation. Herewe describe themolecular cloning fromvascular smoothmuscle, thestructure, andthe chromosomal location ofa diverged homeobox gene,Gax,whoseexpression islargely confined tothe cardiovascular tissues oftheadult. Inquiescent adult ratvascular smooth muscle cells, GaxmRNA levels are down-regulated asmuchas15-fold within 2hwhenthese cells areinduced toproliferate withplatelet-derived growth factor (PDGF) orserumgrowth factors. Thisreduction inGaxmRNA istransient, withlevels beginning torise between 8and24hafter mitogen stimulation andreturning tonear normalby24to48h.TheGax down-regulation isdosedependent andcanbecorrelated withthemitogen's ability tostimulate DNAsynthesis. PDGF-AA,a weakmitogen forratvascular smoothmuscle cells, didnotaffect Gaxtranscript levels, while PDGF-ABand-BB,potent mitogens forthese cells, were nearlyaseffective as fetal bovine serum.Theremoval ofserum fromgrowing cells induced Gaxexpression fivefold within 24h.Thesedatasuggest thatGaxislikely tohavea regulatory function intheGo-to-G1 transition ofthecell cycle invascular smoothmuscle cells.