Treatment with 1,25-Dihydroxyvitamin D3 Preserves Glomerular Slit Diaphragm-Associated Protein Expression in Experimental Glomerulonephritis

Abstract

In this study, we investigated the effect of 1,25(OH)₂D₃ on proteinuria and on the alteration of slit diaphragm-associated proteins induced by anti-Thy 1.1 in Wistar rats. Four groups of animals were studied: group I, anti-Thy 1.1 treated rats; group II, anti-Thy1.1 treated group that at day 2, after the onset of overt proteinuria, started the treatment with 1,25(OH)₂D₃; group III, normal control rats injected with vehicle alone; group IV, rats that received only 1,25(OH)₂D₃. At day 2, in group I and II, before the administration of 1,25(OH)₂D₃, protein excretion was significantly increased when compared to controls. Overt proteinuria was maintained until day 14 in group I whereas in group II protein excretion was significantly reduced from day 3 to day 14. Moreover, treatment with 1,25(OH)₂D₃ abrogated podocytes injury, detected as desmin expression and loss of nephrin and zonula occludens-1 (ZO-1), two slit diaphragm-associated proteins, and glomerular polyanion staining, that were observed in group I. In conclusion, these results suggest that 1,25(OH)₂D₃ administrated with a therapeutic regiment may revert proteinuria, counteracting glomerular podocyte injury.