Transforming growth factor (TGF)-beta stimulates hepatic jun-B and fos-B proto-oncogenes and decreases albumin mRNA.
Transforming growth factor-beta (TGF-beta) modulates some components of the acute phase response in hepatic cells. The mechanisms for these actions of TGF-beta are largely unknown. The authors recently found that the decrease in albumin mRNA after TGF-beta 1 treatment required de novo RNA and protein synthesis, suggesting that TGF-beta acts through induction of another gene. The purpose of the current study was to determine whether TGF-beta 1 could regulate the expression of both the jun and fos genes that encode transcriptional regulatory proteins that constitute the AP-1 complex, and to determine whether expression of these genes may be coordinated with the decrease in albumin mRNA. Northern blot hybridization was used to determine levels of specific mRNAs. Transforming growth factor-beta 1 increased the levels of both jun-B and fos-B mRNA by 60 minutes after treatment of mouse hepatoma (BWTG3) cells. When TGF-beta 1 was removed from the media after 4 hours, there was a sustained effect of increased jun-B and decreased albumin mRNA (greater than 48 hours), and the subsequent decrease in jun-B levels coincided with the increase in albumin mRNA. The tumor-promoting phorbol ester (phorbol 12-myristate 13-acetate [PMA]), known to induce jun and fos gene expression, caused increases in jun-B and fos-B that preceded the decrease in albumin mRNA levels at 24 hours. These observations are consistent with our hypothesis that jun-B and fos-B induction may participate in downregulation of albumin synthesis as well as other hepatic responses to TGF-beta.
Beauchamp
R D
RD
Department of Surgery, University of Texas Medical Branch, Galveston 77555.
Sheng
H M
HM
Ishizuka
J
J
Townsend
C M
CM
Thompson
J C
JC
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000418:Albumins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism*; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000493:pharmacokinetics / Q000494:pharmacology*
D000418:Albumins; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D013449:Sulfonamides; D016212:Transforming Growth Factor beta; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate