Acetaldehyde regulates the gene expression of matrix-metalloproteinase-1 and -2 in human fat-storing cells.
Altered degradation of extracellular matrix has been implicated in the pathogenesis of hepatic fibrosis. We studied the effect of acetaldehyde (AcCHO) on gene expression of matrix-metalloproteinase (MMP)-1 (fibroblast type- interstitial collagenase) and MMP-2 (72 kDa gelatinase-type IV collagenase) in comparison with the AcCHO effect on collagen type I and IV synthesis in cultures of fat-storing cells (FSC) isolated from normal human livers. Cultured human FSC expressed single mRNA transcripts (2.7 and 3.2 kb) specific for MMP-1 and MMP-2, respectively. AcCHO inhibited MMP-1 mRNA levels, whereas it stimulated collagen type I mRNA and protein expression. Opposite AcCHO effects were evident on MMP-2 mRNA and collagen IV synthesis, being MMP-2 up-regulated and collagen IV down-regulated. These data suggest that regulation of MMP-1 and MMP-2 genes by AcCHO may contribute to disruption of the normal basement membrane and its replacement with fibrillar collagens 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
Milani
S
S
Schuppan
D
D
Surrenti
C
C
D000079:Acetaldehyde / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D017364:Collagenases / Q000235:genetics*; D005109:Extracellular Matrix / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D020781:Matrix Metalloproteinase 1; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D003094:Collagen; D017364:Collagenases; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D000079:Acetaldehyde