Modulation of collagen synthesis and degradation by retinoids and cytokines in 3T3 L1 preadipocytes.
We previously observed that a retinoid analog can protect against liver parenchymal damage and liver fibrosis, whereas it accelerates liver fibrosis which is not accompanied by any parenchymal damage. To elucidate these conflicting effects, we examined the effects of retinoid in 3T3 L1 preadipocytes as a model of liver stellate cells. Retinoids, including all-trans retinol, all-trans and 9-cis retinoic acids, enhanced the cell growth and the expression of the type I procollagen gene as well as its peptide synthesis, while reducing collagenase activities. Although no retinoid enhanced the transforming growth factor (TGF)-beta 1 mRNA, retinoids may stimulate collagen production through activating TGF-beta, as was recently reported. These results help explain the observation in the liver fibrosis model with no parenchymal damage. In contrast, we also found that interferon (IFN) alpha beta and gamma inhibited cell growth and down-regulated markedly type I procollagen as well as TGF-beta 1 mRNA, suggesting that they suppress by acting directly on extracellular matrix-producing cells.
Numaguchi
S
S
First Department of Internal Medicine, Gifu University School of Medicine.
Okuno
M
M
Moriwaki
H
H
Muto
Y
Y
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011347:Procollagen / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
D016207:Cytokines; D011347:Procollagen; D012333:RNA, Messenger; D012176:Retinoids; D016212:Transforming Growth Factor beta; D003094:Collagen; D007372:Interferons