Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-4-21
pubmed:abstractText
Mesangial cells in diverse glomerular diseases become myofibroblast-like, characterized by activation of smooth muscle alpha-actin (alpha-SMA) expression. In cultured mesangial cells, serum-deprivation markedly increases alpha-SMA expression, cell size, and stress fiber formation. Since stress fibers are assembled from actin monomers, we investigated the hypothesis that alterations in stress fiber formation regulate alpha-SMA expression and hypertrophy. Human mesangial cells were treated with agents that disrupt or stabilize actin stress fibers. Depolymerization of actin stress fibers in serum-deprived cells with actin-depolymerizing agents, cytochalasin B (CytB) and latrunculin B (LatB), or with inhibitors of Rho-kinase, Y-27632 and HA-1077 decreased alpha-SMA mRNA as judged by Northern blot analysis. Western blot analysis showed that CytB also reduced alpha-SMA protein levels. In serum-fed cells, agents that stabilized actin stress fibers, jasplakinolide (Jas) and phalloidin, increased alpha-SMA mRNA and protein. Treatment of human or rat mesangial cells with CytB, LatB, or Y-27632 decreased alpha-SMA promoter activity. In contrast, Jas increased promoter activity 5.6-fold in rat mesangial cells. The presence of an RNA polymerase inhibitor blocked degradation of alpha-SMA mRNA in cells treated with CytB suggesting that destabilization of this message is dependent on a newly transcribed or rapidly degraded factor. Inhibition of actin polymerization by CytB, LatB, Y-27623, and HA-1077 inhibited incorporation of (3)[H]-leucine into newly synthesized protein. Additionally, CytB and LatB decreased cell volume as determined by flow cytometry. Collectively, these results indicate that the state of polymerization of the actin cytoskeleton regulates alpha-SMA expression, hypertrophy, and myofibroblast differentiation in mesangial cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Actins, http://linkedlifedata.com/resource/pubmed/chemical/Bicyclo Compounds, Heterocyclic, http://linkedlifedata.com/resource/pubmed/chemical/Cytochalasin B, http://linkedlifedata.com/resource/pubmed/chemical/Depsipeptides, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Peptides, Cyclic, http://linkedlifedata.com/resource/pubmed/chemical/Phalloidine, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles, http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidines, http://linkedlifedata.com/resource/pubmed/chemical/jasplakinolide, http://linkedlifedata.com/resource/pubmed/chemical/latrunculin B, http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9541
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
195
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
435-45
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12704653-Actin Cytoskeleton, pubmed-meshheading:12704653-Actins, pubmed-meshheading:12704653-Animals, pubmed-meshheading:12704653-Bicyclo Compounds, Heterocyclic, pubmed-meshheading:12704653-Cell Size, pubmed-meshheading:12704653-Cells, Cultured, pubmed-meshheading:12704653-Cytochalasin B, pubmed-meshheading:12704653-Depsipeptides, pubmed-meshheading:12704653-Enzyme Inhibitors, pubmed-meshheading:12704653-Fibroblasts, pubmed-meshheading:12704653-Glomerular Mesangium, pubmed-meshheading:12704653-Humans, pubmed-meshheading:12704653-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:12704653-Myocytes, Smooth Muscle, pubmed-meshheading:12704653-Peptides, Cyclic, pubmed-meshheading:12704653-Phalloidine, pubmed-meshheading:12704653-Phenotype, pubmed-meshheading:12704653-Promoter Regions, Genetic, pubmed-meshheading:12704653-Protein-Serine-Threonine Kinases, pubmed-meshheading:12704653-RNA, Messenger, pubmed-meshheading:12704653-RNA Stability, pubmed-meshheading:12704653-Rats, pubmed-meshheading:12704653-Thiazoles, pubmed-meshheading:12704653-Thiazolidines, pubmed-meshheading:12704653-Transcriptional Activation, pubmed-meshheading:12704653-rho-Associated Kinases
pubmed:year
2003
pubmed:articleTitle
Regulation of the mesangial cell myofibroblast phenotype by actin polymerization.
pubmed:affiliation
Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk 23501, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't