Regulation of undulin synthesis and gene expression in human fat-storing cells by acetaldehyde and transforming growth factor-beta 1: comparison with fibronectin.
Undulin and fibronectin (FN) are large extracellular matrix (ECM) glycoproteins possibly involved in cell-matrix interactions. In this study we analyzed the effect of acetaldehyde and transforming growth factor-beta 1 (TGF-beta 1) on undulin and FN synthesis in cultured fat-storing cells (FSC) isolated from wedge sections of normal human livers. Cultured human FSC expressed two mRNA transcripts (6.5 and 8.5 kb) specific for undulin. Acetaldehyde inhibited both undulin mRNA and protein expression, whereas it had an opposite (stimulatory) effect on FN synthesis. TGF-beta 1 induced a dose-dependent increase of both undulin and FN synthesis in FSC cultures. Furthermore, TGF-beta 1 antagonized the inhibitory effect of acetaldehyde on undulin production and potentiated the stimulatory effect of acetaldehyde on FN synthesis. Since undulin is involved in the supramolecular organization of fibrillar collagens and in their enzymatic degradation, its acetaldehyde-induced inhibition may contribute to ECM rearrangement in the early stages of alcoholic liver fibrosis.
Casini
A
A
Department of Clinical Pathophysiology, University of Florence, Italy.
Ceni
E
E
Salzano
R
R
Schuppan
D
D
Milani
S
S
Pellegrini
G
G
Surrenti
C
C
D000079:Acetaldehyde / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C054447:COL14A1 protein, human; D005353:Fibronectins; D006023:Glycoproteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; D000079:Acetaldehyde