Linked Life Data

17173240

Source:http://linkedlifedata.com/resource/pubmed/id/17173240

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-12-18
pubmed:abstractText
There have been dramatic increases in the understanding of the molecular mechanisms involved in membranous nephropathy (MN) over the past 2 decades. Most of these have come directly from studies carried out in the Heymann nephritis models of MN in rats, which closely simulate the clinical and pathologic features of the human disease. Once considered a prototypical example of circulating immune complex trapping in glomeruli, we now recognize that MN develops, in both the rat and man, consequent to an autoimmune process involving antibodies directed to antigens on the foot processes of podocytes that form subepithelial immune deposits. Proteinuria is a consequence of sublytic complement C5b-9 attack on podocytes. The podocyte response to sublytic C5b-9 includes up-regulated expression of genes for production of oxidants, proteases, prostanoids, growth factors, CTGF, transforming growth factor (TGF) and TGF receptors leading to overproduction of extracellular matrix components that result in 'spike' formations. Other podocyte changes including detachment, apoptosis and alterations in cell cycle regulatory proteins favoring hypertrophy over proliferation also contribute to proteinuria and to development of glomerular sclerosis. Finally, progression of chronic proteinuric MN to chronic kidney disease (CKD) and renal failure likely results in part from additional effects of sublytic C5b-9 on proximal tubular epithelial cells, resulting in interstitial inflammation and fibrosis with a fall in glomerular filtration rate (GFR). Expanded understanding of the molecular pathophysiology of MN has important implications for monitoring disease activity, predicting disease course and designing new approaches to therapy for this common glomerular disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1121-8428
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
699-705
pubmed:meshHeading
pubmed:articleTitle
Cellular and molecular biology of membranous nephropathy.
pubmed:affiliation
Division of Nephrology, University of Washington, Seattle, Washington, USA. wgc@u.washington.edu
pubmed:publicationType
Journal Article, Review