Preconditioning with Endoplasmic Reticulum Stress Ameliorates Mesangioproliferative Glomerulonephritis
- 1 May 2008
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 19 (5), 915-922
- https://doi.org/10.1681/asn.2007070745
Abstract
Accumulating evidence suggests a pathophysiologic role of endoplasmic reticulum (ER) stress in kidney disease. This study investigated the potential of therapeutic approaches targeting ER stress in the anti-Thy1 model of mesangioproliferative glomerulonephritis in rats. Immunohistochemistry and Western blotting showed a time-dependent increase in the expression of the ER stress–inducible chaperones glucose-regulated protein 78 (GRP78) and oxygen-related protein 150 in isolated glomeruli, especially in the glomerular epithelial cells and mesangial cells, after induction of anti-Thy1 nephritis. For evaluation of whether preconditioning with ER stress ameliorates the severity of disease, rats were pretreated with a subnephritogenic dose of the ER stress inducer tunicamycin or thapsigargin for 4 d before disease was induced. Although preconditioning with ER stress had no effect on the degree of disease induction, it strongly ameliorated the manifestations of disease, evidenced by marked reductions in microaneurysm formation, mesangial proliferation, and adhesion of Bowman's capsule to the glomerular tuft. This improvement in histologic damage was associated with reduced proteinuria (39.4 ± 10.5 versus 126.1 ± 18.1 mg/d; P < 0.01) and with attenuated increases in glucose-regulated protein 78 and oxygen-related protein 150 expression. Of note, pretreatment with tunicamycin or thapsigargin decreased the excessive ER stress–induced intracellular signaling observed in anti-Thy1 nephritis. In conclusion, preconditioning with ER stress ameliorates the severity of disease in rats with anti-Thy1 nephritis. These findings suggest the possibility of therapeutic approaches targeting ER stress in mesangioproliferative glomerulonephritis.Keywords
This publication has 36 references indexed in Scilit:
- 4-Phenylbutyrate rescues trafficking incompetent mutant α-galactosidase A without restoring its functionalityBiochemical and Biophysical Research Communications, 2007
- ER chaperones in mammalian development and human diseasesFEBS Letters, 2007
- Ischemia-Induced Neuronal Cell Death and Stress ResponseAntioxidants and Redox Signaling, 2007
- Endoplasmic reticulum chaperones inhibit the production of amyloid-β peptidesBiochemical Journal, 2007
- Mediators of endoplasmic reticulum stress‐induced apoptosisEMBO Reports, 2006
- The effect of dexamethasone on defective nephrin transport caused by ER stress: A potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseasesKidney International, 2006
- Protection of Endothelial Cells by Dextran Sulfate in Rats with Thrombotic MicroangiopathyJournal of the American Society of Nephrology, 2005
- Endoplasmic reticulum stress: cell life and death decisionsJCI Insight, 2005
- Modulating the Endoplasmic Reticulum Stress Response with trans-4,5-Dihydroxy-1,2-Dithiane Prevents Chemically Induced Renal Injury In VivoToxicological Sciences, 2005
- THE MAMMALIAN UNFOLDED PROTEIN RESPONSEAnnual Review of Biochemistry, 2005