Regulation of extracellular matrix synthesis by transforming growth factor beta 1 in human fat-storing cells.
BACKGROUND
Fat storing cells (FSC) are nonparenchymal liver cells generally considered the major source of the hepatic extracellular matrix (ECM). Transforming growth factor beta 1 (TGF-beta 1) is a potent regulator of ECM synthesis in various cell types. In this study, the effect of TGF-beta 1 on procollagen types I, III, IV, laminin (Lam), and fibronectin (FN) synthesis in cultured human FSCs was analyzed.


METHODS
FSCs were isolated from wedge sections of normal human livers. Morphological studies were performed by immunofluorescence and electron microscopy. ECM components in human FSC cultures were measured by an enzyme-linked immunosorbent assay. The expression of messenger RNA (mRNA) was evaluated by Northern blot and in situ hybridization.


RESULTS
Cultured human FSCs displayed numerous fat droplets in the perinuclear zone, and immunoreactivity for vimentin and alpha-smooth muscle actin. A weak nonfibrillar staining was observed by using a polyclonal antidesmin antibody. TGF-beta 1 induced a dose-dependent increase of procollagen I, III, and FN accumulation in human FSC cultures, whereas procollagen IV and Lam production was not affected. Furthermore, TGF-beta 1 increased the expression of alpha 1 (I), alpha 1 (III) procollagen, FN and TGF-beta 1 mRNA in human FSC cultures.


CONCLUSIONS
These data indicate that TGF-beta 1 is able to increase the synthesis of procollagen I, III, and FN in cultured human FSCs. Moreover, TGF-beta 1 can induce its own mRNA in the same cells.
Department of Clinical Pathophysiology, University of Florence, Italy.
A
A
Casini
M
M
Pinzani
S
S
Milani
C
C
Grappone
G
G
Galli
A M
AM
Jezequel
D
D
Schuppan
C M
CM
Rotella
C
C
Surrenti
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D007797:Laminin / Q000096:biosynthesis; D011347:Procollagen / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D011347:Procollagen; D016212:Transforming Growth Factor beta