PMID- 16766579
OWN - NLM
STAT- MEDLINE
DCOM- 20061129
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 291
IP  - 5
DP  - 2006 Nov
TI  - Acidic fibroblast growth factor decreases alpha-smooth muscle actin expression 
      and induces apoptosis in human normal lung fibroblasts.
PG  - L871-9
AB  - Fibroblast/myofibroblast expansion is critical in the pathogenesis of pulmonary 
      fibrosis. To date, most research has focused on profibrotic mediators, whereas 
      studies on antifibrotic factors are scanty. In this study, we explored the 
      effects of acidic fibroblast growth factor (FGF-1) and FGF-1 plus heparin 
      (FGF-1+H) on fibroblast growth rate, apoptosis, and myofibroblast 
      differentiation. Heparin was used because it participates in FGF-1 signaling. 
      Growth rate was evaluated by WST-1 colorimetric assay, DNA synthesis by 
      [(3)H]thymidine incorporation, and apoptosis by terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) and cleaved caspase 3. 
      Expression of alpha-smooth muscle actin (alpha-SMA) was examined by 
      immunocytochemistry, flow cytometry, real-time PCR, and immunoblotting. Despite 
      the induction of DNA synthesis, FGF-1+H significantly reduced fibroblast growth 
      rate. This correlated with a significant increase in apoptosis, evaluated by 
      TUNEL (41.6 +/- 1.4% vs. 12.5 +/- 0.6% from controls; P < 0.01) and cleaved 
      caspase 3 (295 +/- 32 vs. 200 +/- 19 ng/10(6) cells from controls; P < 0.05). 
      Double immunostaining (alpha-SMA-TUNEL) revealed that the levels of induced 
      apoptosis were similar in fibroblasts and myofibroblasts. FGF-1+H inhibited the 
      effect of TGF-beta1 on myofibroblast differentiation. alpha-SMA-positive cells 
      were reduced by immunocytochemistry from 44.5 +/- 6.5% to 10.9 +/- 1.9% and by 
      flow cytometry from 30.6 +/- 2.5% to 7.7 +/- 0.6% (P < 0.01). Also, FGF-1+H 
      significantly inhibited the TGF-beta1 induction of alpha-SMA quantified by 
      real-time PCR and Western blot. This decrease was associated with a 35% reduction 
      in TGF-beta1-induced collagen gel contraction. The effect of FGF-1+H was mediated 
      by a significant decrease of TGF-beta1-induced Smad2 phosphorylation. FGF-1 alone 
      exhibited similar but lower effects. These findings suggest that FGF-1 can have 
      an antifibrogenic role, inducing apoptosis of fibroblasts and inhibiting 
      myofibroblast differentiation.
FAU - Ramos, Carlos
AU  - Ramos C
AD  - Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, CP 14080, Mexico 
      DF, Mexico.
FAU - Montano, Martha
AU  - Montano M
FAU - Becerril, Carina
AU  - Becerril C
FAU - Cisneros-Lira, Jose
AU  - Cisneros-Lira J
FAU - Barrera, Lourdes
AU  - Barrera L
FAU - Ruiz, Victor
AU  - Ruiz V
FAU - Pardo, Annie
AU  - Pardo A
FAU - Selman, Moises
AU  - Selman M
LA  - eng
PT  - Journal Article
DEP - 20060609
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Actins)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Gels)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 10028-17-8 (Tritium)
RN  - 104781-85-3 (Fibroblast Growth Factor 1)
RN  - 9005-49-6 (Heparin)
RN  - 9007-34-5 (Collagen)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Actins/*genetics/metabolism
MH  - Apoptosis/drug effects/*physiology
MH  - Cell Differentiation/drug effects/physiology
MH  - Cell Division/drug effects/physiology
MH  - Cells, Cultured
MH  - Collagen
MH  - Drug Synergism
MH  - Fibrinolytic Agents/pharmacology
MH  - Fibroblast Growth Factor 1/*metabolism/pharmacology
MH  - Fibroblasts/cytology/*physiology
MH  - Gels
MH  - Gene Expression/drug effects/physiology
MH  - Heparin/pharmacology
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Lung/*cytology
MH  - Phenotype
MH  - Phosphorylation/drug effects
MH  - Smad2 Protein/metabolism
MH  - Thymidine/pharmacokinetics
MH  - Transforming Growth Factor beta1/metabolism/pharmacology
MH  - Tritium
EDAT- 2006/06/13 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/06/13 09:00
PHST- 2006/06/13 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/06/13 09:00 [entrez]
AID - 00019.2006 [pii]
AID - 10.1152/ajplung.00019.2006 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2006 Nov;291(5):L871-9. doi: 
      10.1152/ajplung.00019.2006. Epub 2006 Jun 9.