Acute glomerular upregulation of ornithine decarboxylase is not essential for mesangial cell proliferation and matrix expansion in anti-Thy-1-nephritis

Background. Pathways of L-arginine metabolism including nitric oxide, agmat ine and polyamine synthesis are upregulated during glomerular inflammation in experimental glomerulonephritis. In anti-Thy-1-glomerulonephritis L-argi nine-deficient diets ameliorate the disease course in this model. However, it is unclear which metabolic pathway is affected by this substrate depleti on. Since polyamines are important proproliferative molecules, we studied t he effect of specific polyamine synthesis blockade in vitro on mesangial ce ll proliferation and glomerular fibrosis in this model. Methods. Anti-Thy-1-glomerulonephritis was induced in male Sprague-Dawley r ats by single-bolus injection of monoclonal ER4-antibodies. Rats were treat ed with difluoromethylornithine (0.5-2% in the drinking water), a selective inhibitor of the rate-limiting enzyme of polyamine synthesis, ornithine de carboxylase (ODC). Mesangial cell proliferation and matrix expansion were e valuated in PAS-stained kidney tissues. Glomerular TGF-beta and biglycan-mR NA-expression were determined by Northern blot analysis and albuminuria was measured using a competitive ELISA. Data were compared to untreated contro ls. Results. Though complete inhibition of ODC activity was achieved at any tim e point, difluoromethlornithine treatment had no significant effect on albu minuria, glomerular matrix protein expression and mesangial cell count in t his model. Conclusions. The acute upregulation of glomerular ODC activity above baseli ne in anti-Thy-1-glomerulonephritis is not pathophysiologically important f or disease development however, biological effects of available polyamine p ools cannot be excluded by our study.