PMID- 15913806
OWN - NLM
STAT- MEDLINE
DCOM- 20051207
LR  - 20061115
IS  - 0167-0115 (Print)
IS  - 0167-0115 (Linking)
VI  - 130
IP  - 1-2
DP  - 2005 Aug 15
TI  - Targeting TGF-beta1 increases hepatocyte growth factor (HGF/SF) levels in 
      external auditory canal cholesteatoma (EACC) epithelial cell culture.
PG  - 75-80
AB  - OBJECTIVE: The transforming growth factor (TGF)-beta 1 is known to have pro- and 
      anti-angiogenic actions. Hepatocyte growth factor/scatter factor (HGF/SF) 
      antagonizes TGF-beta1 by stabilizing SMAD transcriptional co-repressor TGIF. 
      HGF/SF is a multifunctional polypeptide with morphogenic, motogenic, angiogenic, 
      and proliferative capabilities. We assume HGF to be a pivotal factor during the 
      pathogenesis of the external auditory canal cholesteatoma (EACC). In this study, 
      we investigate the effect of antisense targeting TGF-beta1 on HGF/SF levels in 
      the epithelial EACC-culture. MATERIALS: For 48 h, epithelial EACC cell culture 
      was incubated with 3 and 6 mumol antisense targeting TGF-beta1, respectively. 
      Levels of HGF/SF were determined and normalized to cellular protein. Untreated 
      EACC cell culture and scrambled TGF-beta1-antisense served as control. In the 
      second experiment, EACC cells were incubated with rh TGF-beta1 (2 and 4 ng/ml) 
      for 48 h and HGF/SF was determined. RESULTS: After incubation with 3 mumol 
      TGF-beta1-antisense, the average level of HGF/SF was measured at 43.68 pg/ml. 
      Incubation with 6 micromol TGF-beta1-antisense showed 64.95 pg/ml. In untreated 
      EACC (control), the average level of HGF/SF after 48 was 34.55 pg/ml. Incubation 
      with scrambled TGF-beta1 oligonucleotide showed an average HGF/SF level of 34.41 
      (3 micromol) and 35.66 (6 micromol), respectively. The difference between the 
      scrambled antisense and the targeting antisense TGF-beta1 was significant 
      (p<0.05). After incubation with 2 ng/ml TGF-beta1, the HGF/SF levels were at 
      22.16 pg/ml. TGF-beta1, 4 ng/ml, resulted in 15.33 pg/ml of HGF/SF. The 
      difference of the levels of HGF/SF after incubation with exogenous TGF-beta1 was 
      significant (p<0.05). CONCLUSION: In this study, levels of HGF/SF increased in 
      the epithelial EACC cell culture after incubation with 3 and 6 mumol antisense 
      TGF-beta1 oligonucleotides depending on the concentration of the antisense. In 
      reverse, TGF-beta1 acted as inhibiting cytokine on HGF/SF levels. In conclusion, 
      TGF-beta1 may be a useful therapeutic agent for managing EACC.
FAU - Naim, Ramin
AU  - Naim R
AD  - Department of Otolaryngology, Head and Neck Surgery, University Hospital 
      Mannheim, Germany.
FAU - Chang, Ray C
AU  - Chang RC
FAU - Alfano, Suzanne S
AU  - Alfano SS
FAU - Riedel, Frank
AU  - Riedel F
FAU - Bayerl, Christiane
AU  - Bayerl C
FAU - Sadick, Haneen
AU  - Sadick H
FAU - Bran, Gregor
AU  - Bran G
FAU - Hormann, Karl
AU  - Hormann K
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Regul Pept
JT  - Regulatory peptides
JID - 8100479
RN  - 0 (Cytokines)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Peptides)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Cholesteatoma/*metabolism
MH  - Cytokines/metabolism
MH  - Ear Canal/metabolism/pathology
MH  - Epithelial Cells/cytology
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Immunoassay
MH  - Keratinocytes/cytology
MH  - Models, Biological
MH  - Oligonucleotides, Antisense/chemistry/pharmacology
MH  - Peptides/chemistry
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Time Factors
MH  - Transforming Growth Factor beta/*metabolism
MH  - Transforming Growth Factor beta1
EDAT- 2005/05/26 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/05/26 09:00
PHST- 2004/11/22 00:00 [received]
PHST- 2005/03/24 00:00 [revised]
PHST- 2005/03/24 00:00 [accepted]
PHST- 2005/05/26 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/05/26 09:00 [entrez]
AID - S0167-0115(05)00115-1 [pii]
AID - 10.1016/j.regpep.2005.03.008 [doi]
PST - ppublish
SO  - Regul Pept. 2005 Aug 15;130(1-2):75-80. doi: 10.1016/j.regpep.2005.03.008.