Tissue-Specific and Developmental Regulation of Transforming Growth Factor-β1Expression in Fetal Lamb Ductus Arteriosus Endothelial Cells
作者:
BIN ZHOU,
CLAIRE COULBER,
MARLENE RABINOVITCH,
期刊:
Pediatric Research
(OVID Available online 1998)
卷期:
Volume 44,
issue 6
页码: 865-872
ISSN:0031-3998
年代: 1998
出版商: OVID
数据来源: OVID
摘要:
We previously established that increased hyaluronan synthesis in ductus arteriosus (DA) compared with aorta (Ao) endothelial cells (EC) from early gestation fetal lambs (100-d, term = 145 d) is transforming growth factor-β (TGF-β)-dependent. We now address whether this is associated with tissue-specific and developmentally up-regulated expression of TGF-β1in the 100-d DA EC. Immunoprecipitation revealed TGF-β synthesis doubled in DAversusAo EC from 100-d gestation lambs (p< 0.05). In 138-d DA EC, TGF-β protein levels were reduced (p< 0.05) and comparable to those in Ao cells. Western immunoblotting with a β1isoform-specific antibody confirmed these differences as being related to TGF-β1. Northern blot analysis demonstrated that TGF-β1mRNA levels were slightly but not significantly increased in 100-d DA compared with Ao EC, despite its short half-life in DA (9.5 h)versusAo EC (20 h). TGF-β1mRNA levels were reduced in 138-d DA and Ao EC (p< 0.05), and the mRNA half-life was comparable in DA (9 h)versusAo (13 h). Nuclear run-on analysis confirmed increased TGF-β1mRNA transcription in 100-d DAversusAo and 138-d DA EC. Thus, up-regulated TGF-β1expression in 100-d DA compared with Ao cells is due to increased transcription and translation of a relatively unstable mRNA, and its down-regulation in 138-d DA and Ao EC is related to reduced mRNA transcription and stability, respectively.
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