PMID- 10381371
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20061115
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 260
IP  - 1
DP  - 1999 Jun 24
TI  - Hepatocyte growth Factor/Scatter factor (HGF/SF) is a regulator of fibronectin 
      splicing in MDCK cells: comparison between the effects of HGF/SF and TGF-beta1 on 
      fibronectin splicing at the EDA region.
PG  - 225-31
AB  - EDA-containing fibronectin (EDA + FN) is selectively produced under several 
      physiological and pathological conditions requiring tissue remodeling, where 
      cells actively proliferate and migrate. Only a few growth factors, such as 
      transforming growth factor (TGF)-beta1, have been reported to regulate FN 
      splicing at the EDA region. In the present study, we showed for the first time 
      that hepatocyte growth factor/scatter factor (HGF/SF), which is mainly produced 
      by mesenchymal cells and functions as a motogenic and mitogenic factor for 
      epithelial cells, modulates FN splicing at the EDA region in MDCK epithelial 
      cells. HGF/SF treatment increased the ratio of EDA + FN mRNA to mRNA of FN that 
      lacks EDA (EDA - FN) (EDA+/EDA- ratio) more than TGF-beta1 treatment did: at a 
      range from 0.02 to 20 ng/ml, HGF/SF increased the ratio in a dose-dependent 
      manner by up to 2. 1-fold compared with nontreated control, while TGF-beta1 
      stimulated the EDA+/EDA- ratio by 1.5-fold at the optimum dose of 10 ng/ml. 
      However, TGF-beta1 increased total FN mRNA levels by 3-fold at 10 ng/ml, but 
      HGF/SF did not. We previously demonstrated that fibroblasts cultured at low cell 
      density expressed more EDA + FN than those at high cell density. The same effect 
      of cell density was also observed in MDCK cells. Furthermore, at low cell 
      density, HGF/SF stimulated EDA inclusion into FN mRNA more effectively than did 
      TGF-beta1, whereas at high cell density, TGF-beta1 was more potent than HGF/SF. 
      Simultaneous treatment of cells with HGF/SF and TGF-beta1 synergistically 
      stimulated EDA inclusion into FN mRNA. This stimulation of EDA inclusion into FN 
      mRNA by HGF/SF led to increased EDA + FN protein production and secretion by 
      cells, which was demonstrated by immunoblotting. Thus, our studies have shown 
      that HGF/SF is an enhancer of EDA inclusion into FN mRNA as is TGF-beta1. 
      However, these two factors were different in their effects at low and high cell 
      densities and also in their effects on total FN mRNA levels.
CI  - Copyright 1999 Academic Press.
FAU - Inoue, T
AU  - Inoue T
AD  - Second Department of Pathology, Miyazaki Medical College, 5200 Kihara, Miyazaki, 
      Kiyotake, 889-1692, Japan.
FAU - Nabeshima, K
AU  - Nabeshima K
FAU - Shimao, Y
AU  - Shimao Y
FAU - Koono, M
AU  - Koono M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (EDA protein, human)
RN  - 0 (Ectodysplasins)
RN  - 0 (Fibronectins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Cell Count
MH  - Cell Line
MH  - Dogs
MH  - Dose-Response Relationship, Drug
MH  - Ectodysplasins
MH  - Fibronectins/*metabolism
MH  - Hepatocyte Growth Factor/pharmacology/*physiology
MH  - Humans
MH  - Membrane Proteins/*pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transforming Growth Factor beta/*pharmacology
EDAT- 1999/06/25 00:00
MHDA- 1999/06/25 00:01
CRDT- 1999/06/25 00:00
PHST- 1999/06/25 00:00 [pubmed]
PHST- 1999/06/25 00:01 [medline]
PHST- 1999/06/25 00:00 [entrez]
AID - S0006-291X(99)90881-1 [pii]
AID - 10.1006/bbrc.1999.0881 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Jun 24;260(1):225-31. doi: 
      10.1006/bbrc.1999.0881.