DIFFERENTIAL REGULATION OF SKELETAL ALPHA-ACTIN TRANSCRIPTION IN CARDIAC-MUSCLE BY 2 FIBROBLAST GROWTH-FACTORS

In cardiac muscle, acidic and basic fibroblast growth factors (aFGF and bFGF) regulate at least five genes in common (including α and β myosin heavy chains, atrial natriuretic factor, and the sarcoplasmic reticulum calcium ATPase), provoking a generalized "fetal" phenotype similar to events in pressure-overload hypertrophy; however, aFGF and bFGF differentially control the striated α-actins. bFGF stimulates and aFGF inhibits skeletal α-actin transcripts associated with the embryonic heart, whereas cardiac α-actin mRNA is inhibited by aFGF but not bFGF. To elucidate mechanisms for these selective and discordant actions of aFGF and bFGF on cardiac muscle, chicken skeletal and cardiac α-actin promoter-driven reporter genes were introduced into neonatal rat cardiac myocytes by electroporation. Skeletal α-actin transcription was selectively stimulated by bFGF, whereas the cardiac α-actin promoter was unaffected. In contrast, aFGF suppressed both transfected α-actin genes. The differential regulation of skeletal α-actin transcription was equivalent with either purified or recombinant FGFs and was observed with 5′ flanking sequences from either nucleotide -202 or -2000 to nucleotide -11. Positive and negative modulation of α-actin transcription by growth factors corresponded accurately to the endogenous genes in all permutations studied. These investigations provide a model for reciprocal control of gene transcription by aFGF vs. bFGF.