MODULATION OF TRANSFORMING GROWTH-FACTOR-BETA RECEPTORS OF RAT LIPOCYTES DURING THE HEPATIC WOUND-HEALING RESPONSE - ENHANCED BINDING AND REDUCED GENE-EXPRESSION ACCOMPANY CELLULAR ACTIVATION IN CULTURE AND IN-VIVO
Sl. Friedman et al., MODULATION OF TRANSFORMING GROWTH-FACTOR-BETA RECEPTORS OF RAT LIPOCYTES DURING THE HEPATIC WOUND-HEALING RESPONSE - ENHANCED BINDING AND REDUCED GENE-EXPRESSION ACCOMPANY CELLULAR ACTIVATION IN CULTURE AND IN-VIVO, The Journal of biological chemistry, 269(14), 1994, pp. 10551-10558
Activation of lipocytes, characterized by increased proliferation and
fibrogenesis, is a central feature of the hepatic wound healing respon
se. We have examined whether modulation of receptors for transforming
growth factor beta (TGF-beta) contributes to the fibrogenic behavior o
f activated lipocytes. Isolated lipocytes were maintained in a quiesce
nt state by culturing the cells in suspension, where they displayed mi
nimal specific binding for TGF-beta 1 and only a small amount of type
III (betaglycan) receptor by affinity labeling. In contrast, lipocytes
activated by growth on uncoated plastic displayed saturable binding o
f TGF-beta 1 (K-d = 28 pM, 7,730 receptors/ cell), and receptors types
I, II, and III. Binding activity in quiescent and activated cells cor
related with responsiveness to TGF-beta 1; TGF-beta 1 induced cellular
fibronectin mRNA expression only in activated and not quiescent cells
. Despite the absence of binding in quiescent cells, type II receptor
was detectable by immunoblot. By RNase protection assay, mRNAs for rec
eptor types II and III were greater in quiescent than activated cells.
In freshly isolated lipocytes from animals with liver injury caused b
y the administration of carbon tetrachloride, a rapid but transient in
crease in mRNA for receptor types I (similar to 3.2 fold), II (similar
to 1.5-fold), and III (similar to 3-fold) was observed, with peaks at
12 h for type I receptor, 1 h for type II receptor, and 6 h for type
III receptor; mRNA induction was followed by down-regulation for all r
eceptors. The modest changes in mRNAs compared with marked alterations
in binding activity during mesenchymal cell activation suggest that T
GF-beta receptors may be regulated in vivo in part by a post-translati
onal mechanism.