PMID- 15333329
OWN - NLM
STAT- MEDLINE
DCOM- 20050106
LR  - 20091119
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 31
IP  - 6
DP  - 2004 Dec
TI  - Transforming growth factor-beta antagonizes alveolar type II cell proliferation 
      induced by keratinocyte growth factor.
PG  - 679-86
AB  - Keratinocyte growth factor (KGF) is a mitogen for rat type II cells and also 
      stimulates differentiation in vitro. Administration of KGF also protects the lung 
      from a variety of injuries and subsequent development of fibrosis. Because 
      transforming growth factor (TGF)-beta has been shown to inhibit epithelial cell 
      proliferation and surfactant protein gene expression in other systems and is 
      thought to be a major effector in pulmonary fibrosis, we sought to determine if 
      TGF-beta would antagonize the effects of KGF in primary cultures of alveolar type 
      II cells. Type II cells were cultured on a matrix of type I collagen and Matrigel 
      in the presence or absence of KGF and/or TGF-beta. KGF alone greatly stimulated 
      proliferation and increased cyclin-dependent kinase (cdk) 2 kinase activity and 
      Retinoblastoma susceptibility gene product (Rb) phosphorylation. Cyclin D1, cdk2, 
      and cdc25A protein levels were increased, and p15(Ink4b) and p27(Kip1) protein 
      levels were decreased. TGF-beta markedly inhibited alveolar epithelial cell 
      proliferation induced by KGF. TGF-beta inhibited cdk2 enzyme activity and Rb 
      phosphorylation and increased p15(Ink4b) protein levels. TGF-beta also inhibited 
      differentiation induced by KGF as measured by secretion of surfactant protein-A 
      into the apical media. In summary, TGF-beta inhibits the proliferative effect of 
      KGF in vitro and may be a biologic antagonist of KGF.
FAU - Zhang, Feijie
AU  - Zhang F
AD  - National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 
      80206, USA.
FAU - Nielsen, Larry D
AU  - Nielsen LD
FAU - Lucas, Joseph J
AU  - Lucas JJ
FAU - Mason, Robert J
AU  - Mason RJ
LA  - eng
GR  - HL-29891/HL/NHLBI NIH HHS/United States
GR  - HL-67671/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040827
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (CDKN2B protein, human)
RN  - 0 (Cdkn2b protein, rat)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p15)
RN  - 0 (FGF7 protein, human)
RN  - 0 (Fgf7 protein, rat)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 126469-10-1 (Fibroblast Growth Factor 7)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - EC 3.1.3.48 (CDC25A protein, human)
RN  - EC 3.1.3.48 (Cdc25a protein, rat)
RN  - EC 3.1.3.48 (cdc25 Phosphatases)
SB  - IM
MH  - Animals
MH  - Cell Cycle Proteins/metabolism
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Cyclin-Dependent Kinase Inhibitor p15
MH  - Cyclin-Dependent Kinases/metabolism
MH  - Fibroblast Growth Factor 7
MH  - Fibroblast Growth Factors/*pharmacology
MH  - Humans
MH  - Male
MH  - Phosphorylation/drug effects
MH  - Pulmonary Alveoli/*cytology/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinoblastoma Protein/metabolism
MH  - Transforming Growth Factor beta/*pharmacology
MH  - Tumor Suppressor Proteins/metabolism
MH  - cdc25 Phosphatases/metabolism
EDAT- 2004/08/31 05:00
MHDA- 2005/01/07 09:00
CRDT- 2004/08/31 05:00
PHST- 2004/08/31 05:00 [pubmed]
PHST- 2005/01/07 09:00 [medline]
PHST- 2004/08/31 05:00 [entrez]
AID - 2004-0182OC [pii]
AID - 10.1165/rcmb.2004-0182OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2004 Dec;31(6):679-86. doi: 10.1165/rcmb.2004-0182OC. 
      Epub 2004 Aug 27.