title: 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.
authors.affiliation: "Kidney and Transplantation"Research Center, Department of Nephrology Dialysis and Transplantation, Annunziata Hospital, via F. Migliori 1, 87100, Cosenza, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Perri
authors.affiliation: "Kidney and Transplantation"Research Center, Department of Nephrology Dialysis and Transplantation, Annunziata Hospital, via F. Migliori 1, 87100, Cosenza, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Vizza
authors.affiliation: "Kidney and Transplantation"Research Center, Department of Nephrology Dialysis and Transplantation, Annunziata Hospital, via F. Migliori 1, 87100, Cosenza, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Lupinacci
authors.affiliation: "Kidney and Transplantation"Research Center, Department of Nephrology Dialysis and Transplantation, Annunziata Hospital, via F. Migliori 1, 87100, Cosenza, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Toteda
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, CS, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Amicis
authors.affiliation: "Kidney and Transplantation"Research Center, Department of Nephrology Dialysis and Transplantation, Annunziata Hospital, via F. Migliori 1, 87100, Cosenza, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Leone
authors.affiliation: "Kidney and Transplantation"Research Center, Department of Nephrology Dialysis and Transplantation, Annunziata Hospital, via F. Migliori 1, 87100, Cosenza, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gigliotti
authors.affiliation: "Kidney and Transplantation"Research Center, Department of Nephrology Dialysis and Transplantation, Annunziata Hospital, via F. Migliori 1, 87100, Cosenza, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Lofaro
authors.affiliation: "Kidney and Transplantation"Research Center, Department of Nephrology Dialysis and Transplantation, Annunziata Hospital, via F. Migliori 1, 87100, Cosenza, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: La Russa
authors.affiliation: "Kidney and Transplantation"Research Center, Department of Nephrology Dialysis and Transplantation, Annunziata Hospital, via F. Migliori 1, 87100, Cosenza, Italy. rbonofi@gmail.com.
authors.forename: Renzo
authors.initials: R
authors.lastname: Bonofiglio
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D019898:Autocrine Communication / Q000187:drug effects*; D001665:Binding Sites; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D009393:Nephritis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; D052242:Adiponectin; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D054419:Receptors, Adiponectin; D014157:Transcription Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: AP-1 transcription factor; Adiponectin; Kidney; NFkB transcription factor; Tumor necrosis factor