PMID- 10594764
OWN - NLM
STAT- Publisher
LR  - 20191120
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 113
IP  - 6
DP  - 1999 Dec
TI  - 001: hepatocyte growth factor/scatter factor inhibits UVB induced apoptosis of 
      human keratinocytes via the PI-3-kinase pathway.
PG  - 1136-7
AB  - UVB-irradiation induces apoptosis in primary keratinocytes (KC) and KC-derived 
      cell-lines A431 and HaCaT. Here we report on the inhibition of UV induced 
      KC-apoptosis by hepatocyte growth factor/scatter factor (HGF/SF). The protective 
      effect of HGF/SF for UVB-irradiated primary KC was observed at concentrations as 
      low as 1 ng/ml HGF and was confirmed by demonstration of the inhibition of 
      nucleosome-release and the activation of caspase-3. In contrast to the 
      observation with primary KC HGF/SF had no effect on the survival of A431 and 
      HaCaT cells after UVB-irradiation, despite the fact that we could demonstrate 
      that these cells functionally express the HGF/SF receptor c-met. When blocking 
      signalling pathways initiated by c-met, we found that the inhibition of the 
      phosphatidylinositol-3-OH (PI-3) kinase by wortmannin or LY294002 led to a total 
      inhibition of the anti-apoptotic effect of HGF/SF, whereas the blockade of the 
      MAP-kinase pathway by PD90859 had no effect. This represents the first 
      demonstration of an involvement of the PI-3 kinase pathway in the anti-apoptotic 
      effect of HGF/SF. In conclusion, our data demonstrate that HGF/SF is able to 
      rescue KC but not autonomously growing KC cell lines from apoptosis induced by 
      UVB. Since in vivo HGF/SF is produced by mesenchymal cells, this mechanism may 
      represent an important paracrine loop in the skin supporting the survival of KC 
      after UV-injury.
FAU - Mildner, M
AU  - Mildner M
FAU - Eckhart, L
AU  - Eckhart L
FAU - Lengauer, B
AU  - Lengauer B
FAU - Tschachler, E
AU  - Tschachler E
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
EDAT- 1999/12/14 00:00
MHDA- 1999/12/14 00:00
CRDT- 1999/12/14 00:00
PHST- 1999/12/14 00:00 [pubmed]
PHST- 1999/12/14 00:00 [medline]
PHST- 1999/12/14 00:00 [entrez]
AID - S0022-202X(15)40712-2 [pii]
AID - 10.1046/j.1523-1747.1999.00815.x [doi]
PST - ppublish
SO  - J Invest Dermatol. 1999 Dec;113(6):1136-7. doi: 10.1046/j.1523-1747.1999.00815.x.