DIFFERENTIAL SPLICING OF FIBRONECTIN PREMESSENGER RIBONUCLEIC-ACID DURING CARDIAC ONTOGENY AND DEVELOPMENT OF HYPERTROPHY IN THE RAT

BACKGROUND: Fibronectin, an extracellular matrix protein, exists as mu ltiple isoforms expressed in a time- and cell-dependent manner. Since the developmental pattern of fibronectin expression has not been deter mined in the heart, the first issue of this study was to investigate t he expression of total fibronectin mRNA as well as its isoforms during cardiac ontogeny. In adults, pressure overload induces a shift toward s the fetal form of proteins expressed by either muscle or nonmuscle c ardiac cells. Fetal forms of fibronectin mRNA being found in smooth an d nonmuscle cardiac cells soon after imposition of pressure overload, the pattern of fibronectin expression during the development of pathol ogical growth was analyzed to determine whether the two conditions of cardiac growth resulted in an identical pattern of fibronectin express ion. EXPERIMENTAL DESIGN: Total RNA were isolated from rat heart (a) d uring in utero and postnatal life and (b) at varying periods of time a fter imposition of a pressure overload induced by coarctation of the t horacic aorta in 25-day-old rats. Fibronectin-EIIIA(+) or -EIIIB(+) an d total fibronectin mRNAs were quantitated by reverse transcription-po lymerase chain reactions and dot-blot analysis, respectively. RESULTS: Fibronectin mRNA, abundant in the 14-day-old fetal heart, rapidly dec reased during cardiac physiologic growth (>5-fold); no changes in the fibronectin mRNA level was observed during the development of pressure -induced cardiac hypertrophy. The percentages of fibronectin transcrip ts containing EIIIA or EIIIB exons, very high in the early fetal heart (>45%), harmoniously decreased during cardiac maturation (<12%). Aort ic coarctation resulted in an early, transient (12 to 48 hours) and pr eferential expression of fibronectin-EIIIA(+) mRNA (approximate to 40% ). CONCLUSIONS: In rat heart, neither physiologic nor pressure-induced growth requires increased amounts of fibronectin mRNA but the growth conditions specifically modulated the fibronectin pre-mRNA splicing.