Linked Life Data

1357223

Source:http://linkedlifedata.com/resource/pubmed/id/1357223

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1992-11-6
pubmed:abstractText
We investigated the effects of glucose concentration in serum-free media on the proliferative growth response of a cultured murine mesangial cell line. Raising the ambient D-glucose concentration from 100 mg/dl to 450 mg/dl stimulated cell proliferation after 24 to 48 hours but had a growth inhibitory effect after 72 to 96 hours of incubation. This biphasic proliferative response to high glucose concentration was not mediated by the elevated osmolarity of the medium and did not occur when L-glucose was used. The early phase of glucose-induced proliferation was associated with increased expression of the immediate early genes c-myc and egr-1 as well as with induction of the S-phase related proliferating nuclear cell antigen (PCNA). Several lines of evidence indicated that the late phase of glucose-induced growth inhibition was mediated by the bioactivation of endogenous transforming growth factor beta (TGF-beta). Neutralizing antibody against TGF-beta prevented the late inhibitory effects of glucose on proliferation. On the other hand, exogenous TGF-beta (1 ng/ml) significantly inhibited basal proliferation in mesangial cells. Furthermore, Northern blot analysis revealed that TGF-beta 1 mRNA was induced by 450 mg/dl glucose in the medium after 48 to 72 hours, but not after 24 hours. Cell cycle analysis demonstrated that mesangial cells incubated in high glucose for 24 hours have a higher percentage of cells in the S-G2 phase of the cell cycle compared with cells grown in normal glucose concentration. After 48 hours of culture in elevated glucose concentration, the percentage of cells in S-G2 phase was decreased, and became comparable to that of cells in normal glucose concentration. However, the addition of neutralizing anti-TGF-beta antibody stimulated the progression of cells towards S-G2 in high glucose medium after 48 hours. The findings of this study demonstrate a biphasic growth response of mesangial cells when they were cultured in high glucose concentration; initially there was a transient stimulation of replication for 24 to 48 hours followed by a sustained inhibition after longer incubation periods. This inhibition may be mediated by the glucose-induced synthesis and/or bioactivation of TGF-beta which can inhibit proliferation of mesangial cells in an autocrine fashion.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0085-2538
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
647-56
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
High glucose-induced proliferation in mesangial cells is reversed by autocrine TGF-beta.
pubmed:affiliation
Department of Medicine, University of Pennsylvania, Philadelphia.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.