RESTRICTED EXPRESSION OF HOMEOBOX GENES DISTINGUISHES FETAL FROM ADULT HUMAN SMOOTH-MUSCLE CELLS

Smooth muscle cell plasticity is considered a prerequisite for atheros clerosis and restenosis following angioplasty and bypass surgery, Iden tification of transcription factors that specify one smooth muscle cel l phenotype over another therefore may be of major importance in under standing the molecular basis of these vascular disorders, Homeobox gen es exemplify one class of transcription factors that could govern smoo th muscle cell phenotypic diversity, Accordingly, we screened adult an d fetal human smooth muscle cell cDNA libraries with a degenerate olig onucleotide corresponding to a highly conserved region of the homeodom ain with the idea that homeobox genes, if present, would display a smo oth muscle cell phenotype-dependent pattern of expression, No homeobox genes were detected in the adult human smooth muscle cell library; ho wever, five nonparalogous homeobox genes were uncovered from the fetal library (HoxA5, HoxA11, HoxB1, HoxB7, and HoxC9). Northern blotting o f adult and fetal tissues revealed low and restricted expression of al l five homeobox genes. No significant differences in transcripts of Ho xA5, HoxA11, and HoxB1 were detected between adult or fetal human smoo th muscle cells in culture, HoxB7 and HoxC9, however, showed preferent ial mRNA expression in fetal human smooth muscle cells that appeared t o correlate with the age of the donor, This phenotype-dependent expres sion of homeobox genes was also noted in rat pup versus adult smooth m uscle cells, While similar differences in gene expression have been re ported between subsets of smooth muscle cells from rat vessels of diff erent-aged animals or clones of rat smooth muscle, our findings repres ent a demonstration of a transcription factor distinguishing two human smooth muscle cell phenotypes.