PMID- 8798721
OWN - NLM
STAT- MEDLINE
DCOM- 19961125
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 40
DP  - 1996 Oct 4
TI  - Mechanisms of hepatocyte growth factor stimulation of keratinocyte 
      metalloproteinase production.
PG  - 24576-82
AB  - Matrix metalloproteinases participate in normal physiologic processes; however, 
      their overproduction has been associated with connective tissue destruction in a 
      variety of pathological states. Migrating basal keratinocytes transiently express 
      collagenase-1 during normal cutaneous reepithelialization. However, the 
      overexpression of both collagenase-1 and stromelysin-1 has been associated with 
      the pathogenesis of chronic nonhealing ulcers. Aberrant expression of 
      metalloproteinases in inflammation is mediated, at least in part, by soluble 
      factors. Since hepatocyte growth factor/scatter factor (HGF/SF) has been reported 
      to promote keratinocyte migration and proliferation, key events in wound repair, 
      and since HGF/SF is produced by dermal fibroblasts and its c-Met receptor is 
      expressed by basal keratinocytes in wounded skin, we have studied the effects of 
      HGF/SF upon keratinocyte metalloproteinase expression. We have found that HGF/SF 
      can stimulate keratinocyte collagenase-1 and stromelysin-1 production in a 
      dose-dependent and matrix-dependent manner. Expression of 92-kDa gelatinase was 
      not affected by HGF/SF. We determined that HGF/SF regulation of collagenase-1 
      expression is transcriptionally mediated and requires tyrosine kinase and protein 
      kinase C activaties. HGF/NK1, a naturally occurring, truncated form of HGF/SF, 
      also stimulates collagenase-1 production, but much less efficiently than does the 
      parent molecule. However, HGF/NK2, another HGF/SF splice variant, as well as 
      heparin, potently inhibit HGF/SF-induced collagenase-1 synthesis. These results 
      indicate that HGF/SF and its naturally occurring splice variants have diverse 
      biological effects on keratinocytes and suggest an additional mechanism whereby 
      HGF/SF may regulate keratinocyte function during wound repair.
FAU - Dunsmore, S E
AU  - Dunsmore SE
AD  - Department of Medicine (Dermatology), Washington University School of Medicine, 
      St. Louis, Missouri 63110, USA.
FAU - Rubin, J S
AU  - Rubin JS
FAU - Kovacs, S O
AU  - Kovacs SO
FAU - Chedid, M
AU  - Chedid M
FAU - Parks, W C
AU  - Parks WC
FAU - Welgus, H G
AU  - Welgus HG
LA  - eng
GR  - 5T32AR07284/AR/NIAMS NIH HHS/United States
GR  - AR35805/AR/NIAMS 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 Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9005-49-6 (Heparin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Adult
MH  - Cells, Cultured
MH  - Collagenases/*biosynthesis
MH  - Heparin/pharmacology
MH  - Hepatocyte Growth Factor/antagonists & inhibitors/*pharmacology
MH  - Humans
MH  - Keratinocytes/*drug effects/enzymology
MH  - Matrix Metalloproteinase 3/*biosynthesis
MH  - Protein Kinase C/metabolism
MH  - Protein-Tyrosine Kinases/metabolism
EDAT- 1996/10/04 00:00
MHDA- 1996/10/04 00:01
CRDT- 1996/10/04 00:00
PHST- 1996/10/04 00:00 [pubmed]
PHST- 1996/10/04 00:01 [medline]
PHST- 1996/10/04 00:00 [entrez]
AID - S0021-9258(18)40044-0 [pii]
AID - 10.1074/jbc.271.40.24576 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 Oct 4;271(40):24576-82. doi: 10.1074/jbc.271.40.24576.