PMID- 10777703 OWN - NLM STAT- MEDLINE DCOM- 20000612 LR - 20131121 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 271 IP - 1 DP - 2000 Apr 29 TI - Mechanism of regulation of HGF/SF gene expression in fibroblasts by TGF-beta1. PG - 203-11 AB - The effect of transforming growth factor beta 1 (TGF-beta1) on levels of hepatocyte growth factor/scatter factor (HGF/SF) gene transcripts was investigated in the human lung embryonic fibroblast cell line, MRC-5. TGF-beta1 markedly reduced the expression of the 6. 0-kb and 3.0-kb HGF/SF mRNA, which encode full-length HGF/SF, but it had little effect on the expression of the alternatively spliced 1. 5-kb mRNA, which encodes NK2, a competitive HGF/SF antagonist. Using actinomycin D to block RNA synthesis, it was observed that TGF-beta1 had little effect on the stability of the 1.5-kb NK2 mRNA but increased the rate of degradation of the 6.0- and 3.0-kb HGF/SF mRNA transcripts by a mechanism that was dependent on new protein synthesis. TGF-beta1 minimally increased rather than reduced HGF/SF promoter activity in cells transiently transfected with chloramphenicol acetyltransferase (CAT) reporter genes driven by HGF/SF gene 5'-flanking sequences. In MRC-5 cells, TGF-beta1 modulates HGF/SF gene transcripts at the posttranscriptional level in order to favour expression of the 1.5-kb mRNA that encodes the truncated protein NK2. CI - Copyright 2000 Academic Press. FAU - Harrison, P AU - Harrison P AD - Institute of Liver Studies, GKT School of Medicine, King's Denmark Hill Campus, Bessemer Road, London, SE5 9PJ, United Kingdom. FAU - Bradley, L AU - Bradley L FAU - Bomford, A AU - Bomford A LA - eng PT - Journal Article PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (3' Untranslated Regions) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (Recombinant Proteins) RN - 0 (Transforming Growth Factor beta) RN - 1CC1JFE158 (Dactinomycin) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 98600C0908 (Cycloheximide) RN - EC 3.1.- (Ribonucleases) RN - EC 3.2.1.23 (beta-Galactosidase) SB - IM MH - 3' Untranslated Regions MH - Blotting, Northern MH - Cell Line MH - Cloning, Molecular MH - Cycloheximide/pharmacology MH - Dactinomycin/pharmacology MH - Dose-Response Relationship, Drug MH - Fibroblasts/*metabolism MH - *Gene Expression Regulation, Developmental MH - Hepatocyte Growth Factor/genetics/*metabolism MH - Humans MH - Promoter Regions, Genetic MH - Protein Synthesis Inhibitors/pharmacology MH - Recombinant Proteins/metabolism MH - Ribonucleases/metabolism MH - Time Factors MH - Transforming Growth Factor beta/*pharmacology MH - beta-Galactosidase/metabolism EDAT- 2000/04/25 09:00 MHDA- 2000/06/17 09:00 CRDT- 2000/04/25 09:00 PHST- 2000/04/25 09:00 [pubmed] PHST- 2000/06/17 09:00 [medline] PHST- 2000/04/25 09:00 [entrez] AID - S0006-291X(00)92612-3 [pii] AID - 10.1006/bbrc.2000.2612 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2000 Apr 29;271(1):203-11. doi: 10.1006/bbrc.2000.2612.