Linked Life Data

11433229

Source:http://linkedlifedata.com/resource/pubmed/id/11433229

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-7-2
pubmed:abstractText
Advanced glycosylation end products (AGE) seem to be implicated in the pathogenesis of diabetic nephropathy. The present study has examined the effects of AGE on protein kinase C (PKC) activity and transforming growth factor-beta1 (TGF-beta1) in relation to collagen gene regulation in cultured human mesangial cells (HMCs). Quiescent HMCs were exposed to serum-free media containing bovine serum albumin (BSA), AGE-modified BSA (AGE-BSA), or glycated BSA in which AGE formation was prevented by the use of aminoguanidine (BSA-AM). AGE-BSA (200 microg/mL) induced a peak membrane-associated PKC activity, particularly PKC-a, at 4 hours. AGE-BSA stimulated alpha1(I) and alpha1(IV) collagen mRNA expression after 24-hour incubation with HMCs, which remained elevated until hour 60. HMCs incubated with AGE-BSA induced a significant inhibition of cell proliferation compared with cells incubated with BSA. AGE-BSA stimulated TGF-beta mRNA and protein expression in HMCs. The TGF-beta secreted by HMCs was shown by CCL-64 mink lung cell assay to be bioactive. In contrast, BSA-AM did not affect either collagen or TGF-beta mRNA or protein expression in HMCs. The stimulatory effects of AGE-BSA on collagen gene regulation in HMCs could be negated by the pretreatment of HMCs with GF 109203X for 30 minutes or with phorbol myristate acetate for 24 hours before AGE-BSA administration. Neutralizing antibody to TGF-beta inhibited increased collagen mRNA expression by HMCs exposed to AGE-BSA. These results suggest that AGE-BSA stimulates collagen mRNA expression by activating PKC and the transcriptional upregulation of TGF-beta1 in HMCs. Thus, PKC and TGF-beta may function as key signaling intermediaries in the AGE-up-regulated collagen gene expression pathway in HMCs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2143
pubmed:author
pubmed:issnType
Print
pubmed:volume
138
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
59-68
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11433229-Adult, pubmed-meshheading:11433229-Blotting, Northern, pubmed-meshheading:11433229-Cell Division, pubmed-meshheading:11433229-Cells, Cultured, pubmed-meshheading:11433229-Collagen, pubmed-meshheading:11433229-Enzyme Activation, pubmed-meshheading:11433229-Gene Expression, pubmed-meshheading:11433229-Glomerular Mesangium, pubmed-meshheading:11433229-Glycosylation End Products, Advanced, pubmed-meshheading:11433229-Humans, pubmed-meshheading:11433229-Immunoglobulin G, pubmed-meshheading:11433229-Protein Kinase C, pubmed-meshheading:11433229-RNA, Messenger, pubmed-meshheading:11433229-Serum Albumin, Bovine, pubmed-meshheading:11433229-Signal Transduction, pubmed-meshheading:11433229-Transcription, Genetic, pubmed-meshheading:11433229-Transforming Growth Factor beta
pubmed:year
2001
pubmed:articleTitle
Advanced glycosylation end products stimulate collagen mRNA synthesis in mesangial cells mediated by protein kinase C and transforming growth factor-beta.
pubmed:affiliation
Department of Pathology, Seoul National University College of Medicine, Chongno-gu, Yongon-dong 28, Seoul 110-799, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't