PMID- 7688769
OWN - NLM
STAT- MEDLINE
DCOM- 19930915
LR  - 20181130
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 92
IP  - 2
DP  - 1993 Aug
TI  - Keratinocyte growth factor and hepatocyte growth factor/scatter factor are 
      heparin-binding growth factors for alveolar type II cells in 
      fibroblast-conditioned medium.
PG  - 969-77
AB  - Epithelial-mesenchymal interactions mediate aspects of normal lung growth and 
      development and are important in the restoration of normal alveolar architecture 
      after lung injury. To determine if fibroblasts are a source of soluble growth 
      factors for alveolar type II cells, we investigated the effect of 
      fibroblast-conditioned medium (CM) on alveolar type II cell DNA synthesis. 
      Serum-free CM from confluent adult human lung fibroblasts was concentrated 
      fivefold by lyophilization. Type II cells were isolated from adult rats by 
      elastase dissociation and incubated with [3H]thymidine and varying dilutions of 
      concentrated CM and serum from day 1 to 3 of culture. Stimulation of type II cell 
      DNA synthesis by fibroblast-CM was maximal after 48 h of conditioning and 
      required the presence of serum. The activity of the CM was eliminated by boiling 
      and by treatment with trypsin, pepsin, or dithiothreitol and was additive with 
      saturating concentrations of acidic fibroblast growth factor, epidermal growth 
      factor, and insulin. The growth factor activity bound to heparin-Sepharose and 
      was eluted with 0.6 and 1.0 M NaCl. Neutralizing antibody studies demonstrated 
      that the primary mitogens isolated in the 0.6 and 1.0 M NaCl fractions were 
      keratinocyte growth factor (KGF, fibroblast growth factor 7) and hepatocyte 
      growth factor/scatter factor (HGF/SF), respectively. HGF/SF was demonstrated in 
      the crude CM and KGF was detected in the 0.6 M NaCl eluent by immunoblotting. 
      Northern blot analysis confirmed that the lung fibroblasts expressed both KGF and 
      HGF/SF transcripts. Human recombinant KGF and HGF/SF induced a concentration- and 
      serum-dependent increase in rat alveolar type II cell DNA synthesis. We conclude 
      that adult human lung fibroblasts produce at least two soluble heparin-binding 
      growth factors, KGF and HGF/SF, which promote DNA synthesis and proliferation of 
      rat alveolar type II cells in primary culture. KGF and HGF/SF may be important 
      stimuli for alveolar type II cell proliferation during lung growth and after lung 
      injury.
FAU - Panos, R J
AU  - Panos RJ
AD  - Department of Medicine, Northwestern University Medical School, Chicago, Illinois 
      60611.
FAU - Rubin, J S
AU  - Rubin JS
FAU - Csaky, K G
AU  - Csaky KG
FAU - Aaronson, S A
AU  - Aaronson SA
FAU - Mason, R J
AU  - Mason RJ
LA  - eng
GR  - HL-27353/HL/NHLBI NIH HHS/United States
GR  - HL-29891/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (FGF7 protein, human)
RN  - 0 (Fgf7 protein, rat)
RN  - 0 (Fibroblast Growth Factor 10)
RN  - 0 (Growth Substances)
RN  - 0 (Insulin)
RN  - 104781-85-3 (Fibroblast Growth Factor 1)
RN  - 126469-10-1 (Fibroblast Growth Factor 7)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9007-49-2 (DNA)
SB  - IM
EIN - J Clin Invest 1994 Mar;93(3):1347
MH  - Animals
MH  - Cell Communication
MH  - Cell Division
MH  - Cells, Cultured
MH  - Culture Media, Conditioned
MH  - Culture Media, Serum-Free
MH  - DNA/biosynthesis
MH  - Epidermal Growth Factor/pharmacology
MH  - Fibroblast Growth Factor 1/pharmacology
MH  - Fibroblast Growth Factor 10
MH  - Fibroblast Growth Factor 7
MH  - *Fibroblast Growth Factors
MH  - Fibroblasts/cytology/*physiology
MH  - Growth Substances/biosynthesis/*metabolism/*pharmacology
MH  - Hepatocyte Growth Factor/biosynthesis/*metabolism/pharmacology
MH  - Humans
MH  - Insulin/pharmacology
MH  - Kinetics
MH  - Lung/cytology/*physiology
MH  - Pulmonary Alveoli/cytology/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC294937
EDAT- 1993/08/01 00:00
MHDA- 1993/08/01 00:01
PMCR- 1993/08/01
CRDT- 1993/08/01 00:00
PHST- 1993/08/01 00:00 [pubmed]
PHST- 1993/08/01 00:01 [medline]
PHST- 1993/08/01 00:00 [entrez]
PHST- 1993/08/01 00:00 [pmc-release]
AID - 10.1172/JCI116673 [doi]
PST - ppublish
SO  - J Clin Invest. 1993 Aug;92(2):969-77. doi: 10.1172/JCI116673.