Linked Life Data

11756339

Source:http://linkedlifedata.com/resource/pubmed/id/11756339

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-12-28
pubmed:abstractText
Mesangial cells isolated from NOD mice after the onset of diabetes have undergone a stable phenotypic change. This phenotype is characterized by increased expression of IGF-I and downregulation of collagen degradation, which is associated with decreased MMP-2 activity. Here, we investigated the IGF-I signaling pathway in mesangial cells isolated from NOD mice before (nondiabetic NOD mice [ND-NOD]) and after (diabetic NOD mice [D-NOD]) the onset of diabetes. We found that the IGF-I signaling pathway in D-NOD cells was activated by autocrine IGF-I. They had phosphorylation of the IGF-I receptor beta-subunit, phosphorylation of insulin receptor substrate (IRS)-1, and association of the p85 subunit (phosphatidylinositol 3-kinase [PI3K]) with the IGF-I receptor and IRS-1 in D-NOD cells in the basal state. This was also associated with increased phosphorylation of ERK2 in D-NOD mesangial cells. Inhibiting autocrine IGF-I from binding to its receptor using an IGF-I-neutralizing antibody or inhibiting IGF-I signaling pathways using a specific PI3K inhibitor or a specific mitogen-activated protein kinase/extracellular response kinase kinase inhibitor decreased phosphorylated ERKs in D-NOD cells. Importantly, this was associated with increased MMP-2 activity. The addition of exogenous IGF-I to ND-NOD activated signal transduction. Therefore, we conclude that the IGF-I signaling pathway is intact in both D-NOD and ND-NOD cells. However, the phenotypic change in D-NOD cells is associated with constitutive activation of the IGF-I signaling pathways, which may participate in the development and progression of diabetic glomerulosclerosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
182-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11756339-Analysis of Variance, pubmed-meshheading:11756339-Animals, pubmed-meshheading:11756339-Cell Culture Techniques, pubmed-meshheading:11756339-Cell Line, pubmed-meshheading:11756339-Diabetes Mellitus, Type 1, pubmed-meshheading:11756339-Enzyme Inhibitors, pubmed-meshheading:11756339-Glomerular Mesangium, pubmed-meshheading:11756339-Insulin-Like Growth Factor I, pubmed-meshheading:11756339-MAP Kinase Signaling System, pubmed-meshheading:11756339-Matrix Metalloproteinases, pubmed-meshheading:11756339-Mice, pubmed-meshheading:11756339-Mice, Inbred NOD, pubmed-meshheading:11756339-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:11756339-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:11756339-Mitogen-Activated Protein Kinases, pubmed-meshheading:11756339-Phosphorylation, pubmed-meshheading:11756339-Receptor, IGF Type 1, pubmed-meshheading:11756339-Reference Values, pubmed-meshheading:11756339-Signal Transduction
pubmed:year
2002
pubmed:articleTitle
Autocrine activation of the IGF-I signaling pathway in mesangial cells isolated from diabetic NOD mice.
pubmed:affiliation
Physiology Laboratory, University of Toulouse School of Medicine, Toulouse, France.
pubmed:publicationType
Journal Article, Comparative Study