PMID- 11903488
OWN - NLM
STAT- MEDLINE
DCOM- 20020621
LR  - 20190826
IS  - 0014-2972 (Print)
IS  - 0014-2972 (Linking)
VI  - 31
IP  - 12
DP  - 2001 Dec
TI  - Renal proximal tubular cell growth and differentiation are differentially 
      modulated by renotropic growth factors and tyrosine kinase inhibitors.
PG  - 1029-39
AB  - BACKGROUND: The renotropic growth factors (GFs), hepatocyte GF (HGF), epidermal 
      GF (EGF), and insulin-like GF-I (IGF-I) accelerate renal regeneration in animal 
      models after toxic or ischemic injury. These GFs initiate their biological 
      effects on renal tubular cells by interaction with specific transmembrane 
      receptor tyrosine kinases. MATERIALS AND METHODS: In the proximal tubular cell 
      line PT-1, the biological effects of HGF, EGF, and IGF-I and the 
      growth-inhibitory effects of different tyrosine kinase inhibitors (TKIs) were 
      investigated. Receptor binding and tyrosine kinase phosphorylation were 
      determined by ligand binding studies and Western blot analysis. RESULTS: HGF, 
      EGF, and IGF-I bound with nanomolar affinity to their specific cell membrane 
      receptor tyrosine kinases. In contrast to EGF or IGF-I, HGF induced a variety of 
      cell morphological changes, including cell scattering, formation of tubular 
      structures, and expression of long microvilli on the apical cell membrane. HGF 
      was a 10-fold more potent and more effective growth promoter than EGF or IGF-I. 
      Among the TKIs tested, the mitogenic effect of HGF could be more specifically 
      inhibited by emodin and tyrphostin, that of EGF by methyl-2,5-dihydroxycinnamate, 
      lavendustin A, and genistein, and that of IGF-I by geldanamycin. CONCLUSIONS: In 
      contrast to EGF and IGF-I, HGF stimulated both growth and differentiation of 
      renal proximal tubular cells, demonstrating the amazing biological potency of 
      this renotropic growth factor. Selective TKIs may be a promising approach to 
      modulate diseases with abnormalities in protein kinase signalling pathways such 
      as renal cell carcinoma.
FAU - Ernst, F
AU  - Ernst F
AD  - Division of Nephrology, Department of Internal Medicine II, University of Ulm, 
      Robert-Koch-Strasse 8, D-89081 Ulm, Germany.
FAU - Hetzel, S
AU  - Hetzel S
FAU - Stracke, S
AU  - Stracke S
FAU - Czock, D
AU  - Czock D
FAU - Vargas, G
AU  - Vargas G
FAU - Lutz, M P
AU  - Lutz MP
FAU - Keller, F
AU  - Keller F
FAU - Jehle, P M
AU  - Jehle PM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Clin Invest
JT  - European journal of clinical investigation
JID - 0245331
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Growth Substances)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Receptors, Growth Factor)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Binding, Competitive
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/metabolism/pharmacology
MH  - Growth Substances/metabolism/*pharmacology
MH  - Hepatocyte Growth Factor/metabolism/pharmacology
MH  - Insulin-Like Growth Factor I/metabolism/pharmacology
MH  - Iodine Radioisotopes
MH  - Kidney Tubules, Proximal/*cytology
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors
MH  - Rabbits
MH  - Receptors, Growth Factor/metabolism
EDAT- 2002/03/21 10:00
MHDA- 2002/06/22 10:01
CRDT- 2002/03/21 10:00
PHST- 2002/03/21 10:00 [pubmed]
PHST- 2002/06/22 10:01 [medline]
PHST- 2002/03/21 10:00 [entrez]
AID - 925 [pii]
AID - 10.1046/j.1365-2362.2001.00925.x [doi]
PST - ppublish
SO  - Eur J Clin Invest. 2001 Dec;31(12):1029-39. doi: 
      10.1046/j.1365-2362.2001.00925.x.