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Adiponectin secreted by tubular renal cells during LPS exposure worsens the cellular inflammatory damage

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Abstract

The pathogenetic role of adiponectin (ADPN) in kidney failure is not yet elucidated, since in vitro and in vivo studies have demonstrated that ADPN exerts both anti-inflammatory and pro-inflammatory effects. Starting from our previous findings demonstrating that HK-2 cells express and secrete ADPN, in this study we investigated the autocrine role of ADPN in tubular inflammatory damage induced by lipopolysaccharide (LPS) and the underlying molecular mechanisms. Firstly, we observed that short-term exposure to LPS enhanced ADPN protein expression as well as the adiponectin receptor ADIPOR1 mRNA content together with its signaling pathway downstream, pAMPK/pERK/pJNK, whose up-regulation status was reversed when ADPN gene knockdown occurred. Interestingly, in the same experimental conditions, we observed that ADPN mediated the nuclear translocation of the transcription factors nuclear factor kappa B (NFkB) and pcFos/pcJun (activator protein 1, AP-1), both induced by the pJNK pathway and involved in tumor necrosis factor (TNF)-α transactivation. Indeed, by transient transfection assay, we observed that the LPS-induced increase of TNF-α promoter activity was abrogated in cells pretreated with the inhibitors of NFkB and AP-1. Collectively our results suggest that in HK-2 cells, ADPN produced upon LPS stimulus could worsen the inflammatory damage in an autocrine-dependent manner.

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    Authors and Affiliations

    1. “Kidney and Transplantation”Research Center, Department of Nephrology Dialysis and Transplantation, Annunziata Hospital, via F. Migliori 1, 87100, Cosenza, Italy

      Anna Perri, Donatella Vizza, Simona Lupinacci, Giuseppina Toteda, Francesca Leone, Paolo Gigliotti, Danilo Lofaro, Antonella La Russa & Renzo Bonofiglio

    2. Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, CS, Italy

      Francesca De Amicis

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    1. Anna Perri
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    2. Donatella Vizza
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    3. Simona Lupinacci
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    4. Giuseppina Toteda
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    5. Francesca De Amicis
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    6. Francesca Leone
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    7. Paolo Gigliotti
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    8. Danilo Lofaro
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    10. Renzo Bonofiglio
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    Correspondence to Renzo Bonofiglio.

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    A. Perri and D. Vizza contributed equally to this work.

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    Perri, A., Vizza, D., Lupinacci, S. et al. Adiponectin secreted by tubular renal cells during LPS exposure worsens the cellular inflammatory damage. J Nephrol 29, 185–194 (2016). https://doi.org/10.1007/s40620-015-0220-2

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    • DOI: https://doi.org/10.1007/s40620-015-0220-2

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