Journal of Nephrology

, Volume 29, Issue 2, pp 185–194 | Cite as

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

  • Anna Perri
  • Donatella Vizza
  • Simona Lupinacci
  • Giuseppina Toteda
  • Francesca De Amicis
  • Francesca Leone
  • Paolo Gigliotti
  • Danilo Lofaro
  • Antonella La Russa
  • Renzo Bonofiglio
Original Article

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.

Keywords

Adiponectin Kidney NFkB transcription factor AP-1 transcription factor Tumor necrosis factor 

Notes

Compliance with ethical standards

Conflict of interest

None.

Ethical approval

This study does not contain any studies with animals and humans.

Informed consent

For this type of study formal consent is not required.

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Copyright information

© Italian Society of Nephrology 2015

Authors and Affiliations

  • Anna Perri
    • 1
  • Donatella Vizza
    • 1
  • Simona Lupinacci
    • 1
  • Giuseppina Toteda
    • 1
  • Francesca De Amicis
    • 2
  • Francesca Leone
    • 1
  • Paolo Gigliotti
    • 1
  • Danilo Lofaro
    • 1
  • Antonella La Russa
    • 1
  • Renzo Bonofiglio
    • 1
  1. 1.“Kidney and Transplantation”Research Center, Department of Nephrology Dialysis and TransplantationAnnunziata HospitalCosenzaItaly
  2. 2.Department of Pharmacy, Health and Nutritional SciencesUniversity of CalabriaRendeItaly

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