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

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.

journal_name

J Nephrol

journal_title

Journal of nephrology

authors

Perri A,Vizza D,Lupinacci S,Toteda G,De Amicis F,Leone F,Gigliotti P,Lofaro D,La Russa A,Bonofiglio R

doi

10.1007/s40620-015-0220-2

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

185-194

issue

2

eissn

1121-8428

issn

1724-6059

pii

10.1007/s40620-015-0220-2

journal_volume

29

pub_type

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