Regulation of the α2(I) collagen gene transcription in fat-storing cells derived from a cirrhotic liver
✍ Scribed by Yutaka Inagaki; Sharada Truter; Patricia Greenwel; Marcos Rojkind; Masashi Unoura; Kenichi Kobayashi; Francesco Ramirez
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 826 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Fat-storing cells (FSC) are the main producers of type I collagen in both normal and fibrotic livers. In order to elucidate the molecular mechanisms controlling collagen expression in FSC, we examined the transcription of the a2(I) collagen gene (COLlA2) in two distinct FSC clones, CFSC-2G and CFSC-BH, derived from a single CCL-induced cirrhotic liver. The phenotype of CFSC-2G resembles freshly isolated FSC, whereas that of CFSC-5H mimics activated myofibroblasts. Cell transfection experiments showed that the upstream sequence between nucleotides -378 and -183 is essential for COLlA2 transcription in both FSC clones. This is the same promoter region that is transcriptionally active and contains the binding site of a multimeric protein complex that mediates TGF-p stimulation of COLlA2 expression in dermal fibroblasts. We therefore examined the relative levels of endogenous and transfected COLlA2 transcription and their response to TGF-P treatment in the two FSC clones. The results showed that CFSC-BH expresses a significantly higher level of the COLlA2 mRNA than CFSC-2G. They also showed that TGF-/3 treatment increases both endogenous and transfected COLlA2 transcription in CFSC-2G but not in CFSC-BH. Interestingly, nuclear proteins from both FSC clones bind to the TGF-p-responsive element more strongly than those from dermal fibroblasts. Altogether, the data suggest that collagen production in CFSC-BH cells has been already activated by the autocrine stimulation of TGF-p. In contrast, CFSC-2G cells are only partially activated but can be easily recruited to produce collagen when stimulated by exogenous TGF-P. Thus, we conclude that