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Transforming growth factor-beta receptors in self-limited vs. chronic progressive nephritis in rats.
- Source :
-
The Journal of pathology [J Pathol] 2002 Nov; Vol. 198 (3), pp. 397-406. - Publication Year :
- 2002
-
Abstract
- Increases in transforming growth factor-beta (TGF-beta) expression and extracellular matrix accumulation are transient in acute self-limited mesangial proliferative glomerulonephritis induced by a single injection of anti-thymocyte serum (ATS), while these increases persist following repeated injections that produce chronic progressive sclerosing glomerulonephritis with tubulointerstitial lesions. However, little is known about the expression of TGF-beta receptors (TbetaRs) in cells involved in the proliferative and sclerosing renal lesions. A study of protein and mRNA expression for type I (TbetaRI), type II (TbetaRII), and type III (TbetaRIII) TbetaR in both forms of nephritis was therefore carried out by immunohistochemistry and in situ hybridization. Inhibition of cell proliferation and stimulation of matrix production by TGF-beta1 were assessed in isolated glomeruli using [(3)H]thymidine incorporation and [(3)H]proline metabolic labelling, respectively. In acute self-limited nephritis, expression of TbetaRI, TbetaRII, and TbetaRIII increased in the glomerular and Bowman's capsular epithelial cells comprising the glomerular tuft adhesions to Bowman's capsules. However, TbetaRII expression was not prominent in proliferating mesangial cells. Glomeruli isolated from rats with acute self-limited nephritis at day 7, when mesangial cell proliferation was maximal, were partially resistant to the mitoinhibitory effects of TGF-beta1. In contrast, expression of all three TbetaRs was elevated in glomerular and tubulointerstitial lesions in chronic progressive nephritis, and glomeruli isolated from rats with chronic progressive nephritis 7 days after the second ATS injection were sensitive to TGF-beta1. These data suggest that distinct cellular responses to TGF-beta1 resulting from differential expression of TbetaR underlie the difference between acute self-limited mesangial proliferative and chronic progressive sclerosing ATS nephritis in the development of proliferative and sclerotic renal lesions.<br /> (Copyright 2002 John Wiley & Sons, Ltd.)
- Subjects :
- Acute Disease
Animals
Cell Division
Chronic Disease
Culture Techniques
Disease Progression
Extracellular Matrix drug effects
Extracellular Matrix metabolism
Extracellular Matrix Proteins biosynthesis
Gene Expression
Glomerulonephritis, Membranoproliferative etiology
Glomerulonephritis, Membranoproliferative pathology
Immune Sera
Kidney pathology
Kidney Glomerulus drug effects
Kidney Glomerulus metabolism
Male
Proteinuria etiology
RNA, Messenger genetics
Rats
Rats, Wistar
Receptors, Transforming Growth Factor beta genetics
Transforming Growth Factor beta pharmacology
Glomerulonephritis, Membranoproliferative metabolism
Receptors, Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3417
- Volume :
- 198
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 12375273
- Full Text :
- https://doi.org/10.1002/path.1213