Pioglitazone Enhances the Beneficial Effects of Glucocorticoids in Experimental Nephrotic Syndrome
dc.contributor.author | Agrawal, S | |
dc.contributor.author | Chanley, M | |
dc.contributor.author | Westbrook, D | |
dc.contributor.author | Nie, X | |
dc.contributor.author | Kiato, T | |
dc.contributor.author | Guess, A | |
dc.contributor.author | Benndorf, R. | |
dc.contributor.author | Hidalgo, G | |
dc.contributor.author | Smoyer, W | |
dc.date.accessioned | 2020-04-03T18:40:51Z | |
dc.date.available | 2020-04-03T18:40:51Z | |
dc.date.issued | 2016-05 | |
dc.description.abstract | Glucocorticoids are the primary therapy for nephrotic syndrome (NS), but have serious side effects and are ineffective in ~20-50% of patients. Thiazolidinediones have recently been suggested to be renoprotective, and to modulate podocyte glucocorticoid-mediated nuclear receptor signaling. We hypothesized that thiazolidinediones could enhance glucocorticoid efficacy in NS. We found that puromycin aminonucleoside-induced proteinuria in rats was significantly reduced by both high-dose glucocorticoids (79%) and pioglitazone (61%), but not low-dose glucocorticoids (25%). Remarkably, pioglitazone + low-dose glucocorticoids also reduced proteinuria (63%) comparably to high-dose glucocorticoids, whereas pioglitazone + high-dose glucocorticoids reduced proteinuria to almost control levels (97%). Molecular analysis revealed that both glucocorticoids and pioglitazone enhanced glomerular synaptopodin and nephrin expression, and reduced COX-2 expression, after injury. Furthermore, the glomerular phosphorylation of glucocorticoid receptor and Akt, but not PPARγ, correlated with treatment-induced reductions in proteinuria. Notably, clinical translation of these findings to a child with refractory NS by the addition of pioglitazone to the treatment correlated with marked reductions in both proteinuria (80%) and overall immunosuppression (64%). These findings together suggest that repurposing pioglitazone could potentially enhance the proteinuria-reducing effects of glucocorticoids during NS treatment. | en_US |
dc.identifier.doi | 10.1038/srep24392 | |
dc.identifier.uri | http://hdl.handle.net/10342/7962 | |
dc.title | Pioglitazone Enhances the Beneficial Effects of Glucocorticoids in Experimental Nephrotic Syndrome | en_US |
dc.type | Article | en_US |
ecu.journal.issue | 1 | en_US |
ecu.journal.name | Scientific Reports | en_US |
ecu.journal.volume | 6 | en_US |
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