Stat-3 Signaling Role in an Experimental Model of Nephropathy Induced by Doxorubicin.

Abstract Focal Segmental Glomerulosclerosis (FSGS) is one of the most frequent glomerulopathies, and is considered a public health problem worldwide. FSGS is characterized by glomerular loss mainly due to inflammation and collagen fibers deposition. STAT-3 is a transcription factor associated with cell differentiation, migration and proliferation. Its activation occurs in response to several growth factors and cytokines. In renal cells, STAT-3 has been related with disease progression. Considering this perspective, the present study evaluated the involvement of STAT-3 in an experimental model of FSGS induced by Doxorubicin (DOX). First, we described a novel FSGS model in Swiss mice that after DOX administration showed typical signs of kidney dysfunction like higher proteinuria. Since there were no studies of ADM nephropathy model in heterogeneous mice, we were the first to evaluate the model in this lineage. Control animals treated with STAT-3 inhibitor (STATTIC) presented lower levels of albumin/creatinine ratio, glycosuria e proteinuria while DOX-injected mice showed higher levels. After analyzing some molecules involved in the STAT-3 signaling pathway, it was observed that STAT-3 blockade decreased levels of STAT-3, IL-6 and IL-6R, which remained elevated in DOX-administrated mice. Moreover, we detected that SOCS-3 (a regulator of STAT family) was up-regulated only in STATTIC-treated mice. Finally, histopathological analyzes showed that DOX-treated group had a significant increase in a tubulointerstitial fibrosis and tubular necrosis, which were not identified in both control and STATTIC groups. Thus, our results indicate that STAT-3 can have an important role in experimental FSGS induced by DOX and further studies are encouraged.