B. Zhou et al., TISSUE-SPECIFIC AND DEVELOPMENTAL REGULATION OF TRANSFORMING GROWTH FACTOR-BETA(1) EXPRESSION IN FETAL LAMB DUCTUS-ARTERIOSUS ENDOTHELIAL-CELLS, Pediatric research, 44(6), 1998, pp. 865-872
We previously established that increased hyaluronan synthesis in ductu
s arteriosus (DA) compared with aorta (Ao) endothelial cells (EC) from
early gestation fetal lambs (100-d, term = 145 d) is transforming gro
wth factor-beta (TGF-beta)-dependent. We now address whether this is a
ssociated with tissue-specific and developmentally up-regulated expres
sion of TGF-beta(1) in the 100-d DA EC. Immunoprecipitation revealed T
GF-beta synthesis doubled in DA versus Ao EC from 100-d gestation lamb
s (p < 0.05). In 138-d DA EC, TGF-beta protein levels were reduced (p
< 0.05) and comparable to those in Ao cells. Western immunoblotting wi
th a beta(1) isoform-specific antibody confirmed these differences as
being related to TGF-beta(1). Northern blot analysis demonstrated that
TGF-beta(1) 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-beta(1) 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-beta(1) mRNA transcription in 100-d DA versus Ao and 138-d DA EC.
Thus, up-regulated TGF-beta(1) expression in 100-d DA compared with A
o cells is due to increased transcription and translation of a relativ
ely unstable mRNA, and its down-regulation in 138-d DA and Ao EC is re
lated to reduced mRNA transcription and stability, respectively.