PMID- 1459995
OWN - NLM
STAT- MEDLINE
DCOM- 19930112
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 267
IP  - 35
DP  - 1992 Dec 15
TI  - Negative regulation of hepatocyte growth factor gene expression in human lung 
      fibroblasts and leukemic cells by transforming growth factor-beta 1 and 
      glucocorticoids.
PG  - 24917-20
AB  - Hepatocyte growth factor (HGF), a mesenchymal-derived factor which regulates 
      growth, motility, and morphogenesis of epithelial and endothelial cells, 
      functions as a hepatotrophic and renotrophic factor for regeneration of the liver 
      and kidney. We have now obtained evidence that transforming growth factor-beta 1 
      (TGF-beta 1) and glucocorticoids are negative regulators for HGF gene expression. 
      When TGF-beta 1 or dexamethasone was added to cultures of MRC-5 human embryonic 
      lung fibroblasts and HL-60 human promyelocytic leukemic cells, the amount of HGF 
      secreted into the culture medium was inhibited to 30-40% of that of control 
      cultures by 10 ng/ml TGF-beta 1 and to 40-50% by 10(-6) M dexamethasone. The 
      inhibitory effect of TGF-beta 1 and dexamethasone on HGF synthesis in MRC-5 cells 
      was additive, thereby suggesting that TGF-beta 1 and dexamethasone exert effects 
      through distinct mechanisms. Hydrocortisone also inhibited HGF synthesis with the 
      same potency as dexamethasone; however, testosterone, estriol, and beta-estradiol 
      had no effect. The rate of HGF synthesis in MRC-5 cells, as measured by pulse 
      labeling with [35S]methionine and subsequent immunoprecipitation, was suppressed 
      to 30-40% of the control with 10 ng/ml TGF-beta 1, and to 30-45% by 10(-6) M 
      dexamethasone. HGF mRNA levels in MRC-5 cells and HL-60 cells were 
      dose-dependently suppressed by TGF-beta 1 and dexamethasone; 10 ng/ml TGF-beta 1 
      suppressed HGF mRNA levels to 32% and 35% of control culture, respectively, in 
      MRC-5 cells and HL-60 cells, and 10(-6) M dexamethasone suppressed to 43% and 
      38%, respectively. Thus, TGF-beta 1 and glucocorticoids seem to inhibit HGF 
      synthesis by suppressing the expression of the HGF gene. We propose that a 
      negative regulation of HGF gene expression by TGF-beta 1 or glucocorticoids may 
      be involved in physiological or pathological processes during tissue 
      regeneration.
FAU - Matsumoto, K
AU  - Matsumoto K
AD  - Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
FAU - Tajima, H
AU  - Tajima H
FAU - Okazaki, H
AU  - Okazaki H
FAU - Nakamura, T
AU  - Nakamura T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Glucocorticoids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 3XMK78S47O (Testosterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - FB33469R8E (Estriol)
RN  - FXC9231JVH (Calcitriol)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - CHO Cells
MH  - Calcitriol/pharmacology
MH  - Cell Line
MH  - Cricetinae
MH  - Dexamethasone/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Estradiol/pharmacology
MH  - Estriol/pharmacology
MH  - Fibroblasts
MH  - Gene Expression Regulation/*drug effects
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Glucocorticoids/*pharmacology
MH  - Hepatocyte Growth Factor/*genetics
MH  - Hydrocortisone/pharmacology
MH  - Kinetics
MH  - Leukemia, Promyelocytic, Acute
MH  - Lung
MH  - Prednisolone/pharmacology
MH  - RNA, Messenger/biosynthesis/genetics/isolation & purification
MH  - Recombinant Proteins/pharmacology
MH  - Testosterone/pharmacology
MH  - Transfection
MH  - Transforming Growth Factor beta/genetics/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 1992/12/15 00:00
MHDA- 1992/12/15 00:01
CRDT- 1992/12/15 00:00
PHST- 1992/12/15 00:00 [pubmed]
PHST- 1992/12/15 00:01 [medline]
PHST- 1992/12/15 00:00 [entrez]
AID - S0021-9258(19)73982-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1992 Dec 15;267(35):24917-20.