Linked Life Data

17376761

Source:http://linkedlifedata.com/resource/pubmed/id/17376761

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-7-9
pubmed:abstractText
Connective tissue growth factor (CCN2) is a profibrotic factor acting downstream and independently of TGF-beta to mediate renal fibrosis. Although inflammation is often involved in the initiation and/or progression of fibrosis, the role of inflammatory cytokines in regulation of glomerular CCN2 expression, cellular proliferation, and extracellular matrix accumulation is unknown. We studied two such cytokines, TNF-alpha and IFN-gamma, for their effects on cultured mesangial cells in the presence or absence of TGF-beta, as a model for progressive renal fibrosis. Short-term treatment with TNF-alpha, like TGF-beta, significantly increased secreted CCN2 per cell, but unlike TGF-beta inhibited cellular replication. TNF-alpha combined with TGF-beta further increased CCN2 secretion and mRNA levels and reduced proliferation. Surprisingly, however, TNF-alpha treatment decreased baseline collagen type I protein and mRNA levels and largely blocked their stimulation by TGF-beta. Long-term treatment with TGF-beta or TNF-alpha alone no longer increased CCN2 protein levels. However, the combination synergistically increased CCN2. IFN-gamma had no effect on either CCN2 or collagen activity and produced a mild inhibition of TGF-beta-induced collagen only at a high concentration (500 U/ml). In summary, we report a strong positive regulatory role for TNF-alpha, but not IFN-gamma, in CCN2 production and secretion, including that driven by TGF-beta. The stimulation of CCN2 release by TNF-alpha, unlike TGF-beta, is independent of cellular proliferation and not linked to increased collagen type I accumulation. This suggests that the paradigm of TGF-beta-driven CCN2 with subsequent collagen production may be overridden by an as yet undefined inhibitory mechanism acting either directly or indirectly on matrix metabolism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1931-857X
pubmed:author
pubmed:issnType
Print
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F157-65
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed-meshheading:17376761-Animals, pubmed-meshheading:17376761-Blotting, Northern, pubmed-meshheading:17376761-Cell Proliferation, pubmed-meshheading:17376761-Cells, Cultured, pubmed-meshheading:17376761-Collagen Type I, pubmed-meshheading:17376761-Connective Tissue Growth Factor, pubmed-meshheading:17376761-DNA, Complementary, pubmed-meshheading:17376761-Disease Progression, pubmed-meshheading:17376761-Fibrosis, pubmed-meshheading:17376761-Glomerular Mesangium, pubmed-meshheading:17376761-Immediate-Early Proteins, pubmed-meshheading:17376761-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:17376761-Interferon-gamma, pubmed-meshheading:17376761-Kidney Diseases, pubmed-meshheading:17376761-RNA, Messenger, pubmed-meshheading:17376761-Rats, pubmed-meshheading:17376761-Rats, Inbred F344, pubmed-meshheading:17376761-Transforming Growth Factor beta, pubmed-meshheading:17376761-Tumor Necrosis Factor-alpha
pubmed:year
2007
pubmed:articleTitle
TNF-alpha, but not IFN-gamma, regulates CCN2 (CTGF), collagen type I, and proliferation in mesangial cells: possible roles in the progression of renal fibrosis.
pubmed:affiliation
Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't