Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-10-17
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1523-1747
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2676-85
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
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.
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
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't