Linked Life Data

15930146

Source:http://linkedlifedata.com/resource/pubmed/id/15930146

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-9-13
pubmed:abstractText
Monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor (TGF)-beta1 are critical mediators of renal injury by promoting excessive inflammation and extracellular matrix deposition, thereby contributing to progressive renal disease. In renal disease models, MCP-1 stimulates the production of TGF-beta1. However, a potential role for TGF-beta1 in the regulation of MCP-1 production by mesangial cells (MCs) has not previously been evaluated. The objectives of this study were to define the role of TGF-beta1 in regulation of MCP-1 expression in cultured MCs and to define mechanisms through which rolipram (Rp), a phosphodiesterase isoenzyme 4 (PDE4) inhibitor with anti-inflammatory properties, alters MCP-1 expression. TGF-beta1 induced MCP-1 in a time- and dose-dependent manner without increasing transcription of the MCP-1 gene. TGF-beta1-mediated induction of MCP-1 occurred without activation of the NF-kappaB pathway. Rp blocked TGF-beta1-stimulated MCP-1 expression via a protein kinase A-dependent process, at least in part, by decreasing MCP-1 message stability. Rp exerted no effect on activation of the Smad pathway by TGF-beta1. TGF-beta1-mediated induction of MCP-1 required activation of ERK and p38, both of which were suppressed by a PDE4 inhibitor. TGF-beta1-stimulated reactive oxygen species (ROS) generation by MCs, and Rp inhibited ROS generation in TGF-beta1-stimulated MCs; in addition, both Rp and ROS scavengers blocked TGF-beta1-stimulated MCP-1 expression. We conclude that TGF-beta1 stimulates MCP-1 expression through pathways involving activation of ERK, p38, and ROS generation. Positive cross-talk between TGF-beta1 and MCP-1 signaling in MCs may underlie the development of progressive renal disease. Rp, by preventing TGF-beta1-stimulated MCP-1 production, may offer a therapeutic approach in retarding the progression of renal disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0363-6143
pubmed:author
pubmed:issnType
Print
pubmed:volume
289
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C959-70
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15930146-3',5'-Cyclic-AMP Phosphodiesterases, pubmed-meshheading:15930146-Animals, pubmed-meshheading:15930146-Cell Line, pubmed-meshheading:15930146-Chemokine CCL2, pubmed-meshheading:15930146-Cyclic Nucleotide Phosphodiesterases, Type 4, pubmed-meshheading:15930146-Enzyme Activation, pubmed-meshheading:15930146-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:15930146-Gene Expression, pubmed-meshheading:15930146-Glomerular Mesangium, pubmed-meshheading:15930146-NF-kappa B, pubmed-meshheading:15930146-Rats, pubmed-meshheading:15930146-Reactive Oxygen Species, pubmed-meshheading:15930146-Signal Transduction, pubmed-meshheading:15930146-Transforming Growth Factor beta, pubmed-meshheading:15930146-Transforming Growth Factor beta1, pubmed-meshheading:15930146-p38 Mitogen-Activated Protein Kinases
pubmed:year
2005
pubmed:articleTitle
TGF-beta1 stimulates monocyte chemoattractant protein-1 expression in mesangial cells through a phosphodiesterase isoenzyme 4-dependent process.
pubmed:affiliation
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First St. SW, Stabile 7, Rochester, Minnesota 55905, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural