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http://purl.uniprot.org/citations/15818662http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Objective

To investigate the effects of FK-506 on the expression of the human alpha2(I) collagen gene and transforming growth factor beta (TGFbeta) signaling in normal and scleroderma fibroblasts.

Methods

The expression levels of type I procollagen protein and alpha2(I) collagen messenger RNA (mRNA) were analyzed by immunoblotting and Northern blotting, respectively. The promoter activities of alpha2(I) collagen gene and 3TP-Lux were determined by transient transfection assay. Interaction between TGFbeta receptor type I and FK-506 binding protein 12 (FKBP12) was evaluated by immunoprecipitation.

Results

FK-506 did not affect the basal expression of type I procollagen protein or alpha2(I) collagen mRNA, but it significantly reduced the TGFbeta1-induced expression of type I procollagen protein and alpha2(I) collagen mRNA in normal fibroblasts. The effect of FK-506 was regulated posttranscriptionally, but not transcriptionally. In scleroderma fibroblasts, FK-506 significantly reduced the expression of type I procollagen protein and alpha2(I) collagen mRNA through posttranscriptional regulation, but not transcriptional regulation. FK-506 increased the basal activity of the 3TP-Lux promoter, but it did not affect the TGFbeta1-induced promoter activity in normal fibroblasts. In contrast, FK-506 did not affect the basal or the TGFbeta1-induced 3TP-Lux promoter activity in scleroderma fibroblasts. Furthermore, FKBP12, which protects TGFbeta receptor type I from ligand-independent activation by TGFbeta receptor type II, constitutively dissociated from TGFbeta receptor type I in scleroderma fibroblasts.

Conclusion

FK-506 inhibits alpha2(I) collagen gene expression by reducing the stability of mRNA without exhibiting its activation effect on TGFbeta signaling in scleroderma fibroblasts."xsd:string
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http://purl.uniprot.org/citations/15818662http://purl.uniprot.org/core/author"Asano Y."xsd:string
http://purl.uniprot.org/citations/15818662http://purl.uniprot.org/core/author"Yamane K."xsd:string
http://purl.uniprot.org/citations/15818662http://purl.uniprot.org/core/author"Ihn H."xsd:string
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http://purl.uniprot.org/citations/15818662http://purl.uniprot.org/core/author"Tamaki K."xsd:string
http://purl.uniprot.org/citations/15818662http://purl.uniprot.org/core/author"Mimura Y."xsd:string
http://purl.uniprot.org/citations/15818662http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15818662http://purl.uniprot.org/core/name"Arthritis Rheum"xsd:string
http://purl.uniprot.org/citations/15818662http://purl.uniprot.org/core/pages"1237-1247"xsd:string
http://purl.uniprot.org/citations/15818662http://purl.uniprot.org/core/title"Differential effects of the immunosuppressant FK-506 on human alpha2(I) collagen gene expression and transforming growth factor beta signaling in normal and scleroderma fibroblasts."xsd:string
http://purl.uniprot.org/citations/15818662http://purl.uniprot.org/core/volume"52"xsd:string
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