Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-6-20
pubmed:abstractText
Proliferative vitreoretinopathy (PVR) is one of the major causes of the failure of retinal detachment surgery. Its pathogenesis includes a fibrotic reaction by the retinal pigment epithelium and other retina-derived non-neural cells, leading to fixation of the detached retina. We examined the role of p38 mitogen-activated protein kinase (MAPK) in transforming growth factor (TGF)-beta2-dependent enhancement of the fibrogenic reaction in a human retinal pigment epithelial cell line, ARPE-19, and also evaluated the therapeutic efficacy of inhibiting p38MAPK by adenoviral gene transfer of dominant-negative (DN) p38MAPK in a mouse model of PVR. Exogenous TGF-beta2 activates p38MAPK in ARPE-19 cells. It also suppresses cell proliferation, but this was unaffected by addition of the p38MAPK inhibitor, SB202190. SB202190 interfered with TGF-beta2-dependent cell migration and production of collagen type I and fibronectin, but had no effect on basal levels of these activities. While SB202190 did not affect phosphorylation of the C-terminus of Smads2/3, it did suppress the transcriptional activity of Smads3/4 as indicated by a reporter gene, CAGA12-Luc. Gene transfer of DN-p38MAPK attenuated the post-retinal detachment fibrotic reaction of the retinal pigment epithelium in vivo in mice, supporting its effectiveness in preventing/treating PVR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0023-6837
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
838-50
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15924151-Animals, pubmed-meshheading:15924151-Cell Line, pubmed-meshheading:15924151-Cell Movement, pubmed-meshheading:15924151-Cell Proliferation, pubmed-meshheading:15924151-Collagen Type I, pubmed-meshheading:15924151-Disease Models, Animal, pubmed-meshheading:15924151-Enzyme Inhibitors, pubmed-meshheading:15924151-Fibronectins, pubmed-meshheading:15924151-Fibrosis, pubmed-meshheading:15924151-Gene Therapy, pubmed-meshheading:15924151-Humans, pubmed-meshheading:15924151-Imidazoles, pubmed-meshheading:15924151-Male, pubmed-meshheading:15924151-Mice, pubmed-meshheading:15924151-Mice, Inbred C57BL, pubmed-meshheading:15924151-Pigment Epithelium of Eye, pubmed-meshheading:15924151-Pyridines, pubmed-meshheading:15924151-Signal Transduction, pubmed-meshheading:15924151-Transforming Growth Factor beta, pubmed-meshheading:15924151-Transforming Growth Factor beta2, pubmed-meshheading:15924151-Vitreoretinopathy, Proliferative, pubmed-meshheading:15924151-p38 Mitogen-Activated Protein Kinases
pubmed:year
2005
pubmed:articleTitle
Inhibition of p38MAP kinase suppresses fibrotic reaction of retinal pigment epithelial cells.
pubmed:affiliation
Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama 641-0012, Japan. shizuya@wakayama-med.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't