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STAT-3 signaling role in an experimental model of nephropathy induced by doxorubicin

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Abstract

The focal segmental glomerulosclerosis (FSGS) is one of the most frequent glomerulopathy in the world, being considered a significative public health problem worldwide. The disease is characterized by glomerular loss mainly due to inflammation process and collagen fibers deposition. STAT-3 is a transcription factor associated with cell differentiation, migration and proliferation and in renal cells it has been related with fibrosis, acting on the progression of the lesion. Considering this perspective, the present study evaluated the involvement of STAT-3 molecule in an experimental model of FSGS induced by Doxorubicin (DOX). DOX mimics primary FSGS by causing both glomerular and tubular lesions and the inhibition of the STAT3 pathway leads to a decrease in fibrosis and attenuation of kidney damage. We described here a novel FSGS experimental model in a strain of genetically heterogeneous mice which resembles the reality of FSGS patients. DOX-injected mice presented elevated indices of albuminuria and glycosuria, that were significantly reduced in animals treated with a STAT-3 inhibitor (STATTIC), in addition with a decrease of some inflammatory molecules. 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 pathway possess an important role in experimental FSGS induced by DOX and may be an important molecule to be further investigated.

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The data analyzed during the study is not publically available but can be available on request to corresponding author.

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Funding

Thabata Caroline de Oliveira Santos was supported by a grant of CAPES (Coordenação de aperfeiçoamento de pessoal de nível superior) - Brazil.

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Authors and Affiliations

  1. Renal Physiology Laboratory, Department of Physiology, Federal University of Paraná, Curitiba, State of Paraná, Brazil

    Thabata Caroline de Oliveira Santos, Gabriel Pereira, Anna Gabrielle Gomes Coutinho, Halison Pereira Dos Santos Silva, Ricardo Fernandez Perez & Rafael Luiz Pereira

  2. Federal University South Frontier, Chapecó, State of Santa Catarina, Brazil

    Débora Tavares Resende e Silva

  3. Laboratory of Neurophysiology, Department of Physiology, Federal University of Paraná, Curitiba, State of Paraná, Brazil

    Marcelo M. S. Lima

  4. Laboratory of Cardiovascular Physiology and Pathophysiology, Department of Physiology, Federal University of Paraná, Curitiba, State of Paraná, Brazil

    Fernando Augusto Lavezzo Dias

  5. Laboratory of Clinical and Experimental Immunology, Department of Medicine – Nephrology, Federal University of São Paulo, São Paulo, State of São Paulo, Brazil

    Danilo Cândido de Almeida

  6. Sector of Biological Sciences, Department of Physiology, Federal University of Paraná, Street Coronel Francisco H. dos Santos, 100, Jardim das Americas, Curitiba, State of Paraná, 81531-980, Brazil

    Rafael Luiz Pereira

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  1. Thabata Caroline de Oliveira Santos
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by TCOS, GP. The first draft of the manuscript was written by TCOS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Rafael Luiz Pereira.

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All experimental procedures were carried out following the ethical principles established by the Experimental Brazilian Council (COBEA) and approved by the local Animal Ethics Committee (protocol n°957).

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de Oliveira Santos, T.C., Pereira, G., Coutinho, A.G.G. et al. STAT-3 signaling role in an experimental model of nephropathy induced by doxorubicin. Mol Cell Biochem 478, 981–989 (2023). https://doi.org/10.1007/s11010-022-04574-2

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