TGF-BETA REGULATES EXPRESSION OF TENASCIN ALTERNATIVE-SPLICING ISOFORMS IN FETAL-RAT LUNG

被引:39
作者
ZHAO, Y [1 ]
YOUNG, SL [1 ]
机构
[1] DUKE UNIV, MED CTR, DEPT MED, DURHAM, NC 27710 USA
关键词
TRANSFORMING GROWTH FACTOR-BETA; FETAL LUNG; LUNG DEVELOPMENT; EXTRACELLULAR MATRIX;
D O I
10.1152/ajplung.1995.268.2.L173
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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). The results confirm that regulation of the TN isoform expression in fetal rat lung occurred at the mRNA level. They further indicate that two protein subunits, TN180 and TN230, were derived from two mRNA-splicing variants: one with 7.3 kb containing five FN-III alternative splicing repeats, and one with 6.4 kb containing one FN-III alternative-splicing repeat.
引用
收藏
页码:L173 / L180
页数:8
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