Source:http://linkedlifedata.com/resource/pubmed/id/18496568
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2008-10-17
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pubmed:abstractText |
Cultured human keratinocytes produce matrix metalloproteinase (MMP)-2 and MMP-9. In this study, using small interfering RNA (siRNA) for MMP-2 or MMP-9, we investigated the functions of these two gelatinases in the regulation of survival by measuring growth, differentiation, apoptosis, and migration of cultured keratinocytes. MMP-2 siRNA treatment significantly decreased keratinocyte growth and migration, and stimulated apoptosis fourfold. In addition, MMP-2 siRNA caused a 70% reduction in keratin-14 (K14) and a fourfold increase in K10. In contrast, MMP-9 siRNA treatment exerted opposite effects on cell growth, apoptosis, and K10 expression. MMP-2 appears to act through the ERK MAP kinase and caspase-3 signaling pathways as evidenced by the 53% reduction in the level of phosphorylated ERK1/2 and threefold increase in phosphorylated p38 and stronger staining for active caspase-3 in response to MMP-2 siRNA. Dual fluorescent staining revealed that almost all cultured cells stained positive for MMP-2, with only a few scattered cells being positive for MMP-9. There were considerably more BrdU-positive cells following MMP-9 siRNA treatment, indicating that MMP-9 inhibited proliferation. In conclusion, MMP-2 stimulates keratinocyte survival whereas MMP-9 promotes terminal differentiation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1523-1747
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
128
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2676-85
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18496568-Apoptosis,
pubmed-meshheading:18496568-Cell Differentiation,
pubmed-meshheading:18496568-Cell Movement,
pubmed-meshheading:18496568-Cell Survival,
pubmed-meshheading:18496568-Cells, Cultured,
pubmed-meshheading:18496568-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:18496568-Humans,
pubmed-meshheading:18496568-Keratinocytes,
pubmed-meshheading:18496568-Matrix Metalloproteinase 2,
pubmed-meshheading:18496568-Matrix Metalloproteinase 9,
pubmed-meshheading:18496568-RNA, Small Interfering,
pubmed-meshheading:18496568-Receptor, Epidermal Growth Factor,
pubmed-meshheading:18496568-Signal Transduction
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pubmed:year |
2008
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pubmed:articleTitle |
Autocrine actions of matrix metalloproteinase (MMP)-2 counter the effects of MMP-9 to promote survival and prevent terminal differentiation of cultured human keratinocytes.
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pubmed:affiliation |
Sutton Arthritis Research Laboratories, Department of Rheumatology, Institute of Bone and Joint Research, The University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia. mlxue@med.usyd.edu.au
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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