AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 173-L180, Copyright © 1995 by American Physiological Society
TGF-beta regulates expression of tenascin alternative-splicing isoforms in fetal rat lung
Y. Zhao and S. L. Young
Research Service, Durham Department of Veterans Affairs Medical Center, North Carolina 27705.
Two distinct mRNA-splice isoforms of tenascin (TN) are expressed
differentially during rat lung development. The unique temporal expression
pattern of two TN isoforms suggests the expression of tenascin is strictly
developmentally regulated in rat lung tissue. We investigated molecular
mechanisms which modulate alternative-splicing expression of TN in lung
development. The effect of transforming growth factor-beta 1 (TGF-beta 1)
on regulation of expression of TN isoforms was examined by in vitro lung
explant culture. Immunoblotting with anti-TN antibody detected two TN
polypeptides in rat lung explant culture, the larger [relative molecular
weight (M(r)) 230, TN230] polypeptide and the smaller (M(r) 180, TN180).
TGF-beta 1 markedly induced the TN180 isoform and caused only a moderate
increase of the TN230 isoform. The effects of TGF-beta 1 were shown to be
dose dependent over a physiological range of TGF-beta 1 protein
concentration. The induction of TN isoform biosynthesis by TGF-beta 1 was
detected 12 h after addition of the growth factor, and the effects endured
for up to 48 h at a dose of 5 ng/ml. By reverse transcriptase-polymerase
chain reaction through amplification of the entire fibronectin type III
(FN-III) splicing domain, two distinct TN isoforms were detected in total
RNA isolated from gestational day 21 rat lung explant culture treated with
TGF-beta 1 and from postnatal day 8 rat lung. The larger isoform contained
five FN-III alternative splicing repeats [1,420 base pairs (bp)], but the
shorter splicing isoform lacked four FN-III alternative splicing repeats
(340 bp).(ABSTRACT TRUNCATED AT 250 WORDS)
