TY - JOUR
T1 - Tissue-specific and developmental regulation of transforming growth factor-β1 expression in fetal lamb ductus arteriosus endothelial cells
AU - Zhou, Bin
AU - Coulber, Claire
AU - Rabinovitch, Marlene
PY - 1998/12
Y1 - 1998/12
N2 - 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-β1 in the 100- d DA EC. Immunoprecipitation revealed TGF-β synthesis doubled in DA versus Ao 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 β1 isoform-specific antibody confirmed these differences as being related to TGF-β1. Northern blot analysis demonstrated that TGF-β1 mRNA 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) versus Ao EC (20 h). TGF-β1 mRNA levels were reduced in 138-d DA and Ao EC (p < 0.05), and the mRNA half-life was comparable in DA (9 h) versus Ao (13 h). Nuclear run-on analysis confirmed increased TGF-β1 mRNA transcription in 100-d DA versus Ao and 138-d DA EC. Thus, up-regulated TGF-β1 expression 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.
AB - 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-β1 in the 100- d DA EC. Immunoprecipitation revealed TGF-β synthesis doubled in DA versus Ao 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 β1 isoform-specific antibody confirmed these differences as being related to TGF-β1. Northern blot analysis demonstrated that TGF-β1 mRNA 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) versus Ao EC (20 h). TGF-β1 mRNA levels were reduced in 138-d DA and Ao EC (p < 0.05), and the mRNA half-life was comparable in DA (9 h) versus Ao (13 h). Nuclear run-on analysis confirmed increased TGF-β1 mRNA transcription in 100-d DA versus Ao and 138-d DA EC. Thus, up-regulated TGF-β1 expression 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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U2 - 10.1203/00006450-199812000-00007
DO - 10.1203/00006450-199812000-00007
M3 - Article
C2 - 9853919
AN - SCOPUS:0031757098
SN - 0031-3998
VL - 44
SP - 865
EP - 872
JO - Pediatric Research
JF - Pediatric Research
IS - 6
ER -