title: Emerging role of Lipopolysaccharide binding protein in sepsis-induced acute kidney injury.
abstract: Sepsis remains a serious cause of morbidity and mortality in critically ill patients, with limited therapeutic options available. Of the several disorders connected with sepsis, acute kidney injury (AKI) is one of the major complications. The pathophysiology of sepsis-induced AKI is characterized by severe inflammation in renal parenchyma with endothelial dysfunction, intra-glomerular thrombosis and tubular injury. Endothelial dysfunction is regulated by several mechanisms implicated in cellular de-differentiation, such as endothelial-to-mesenchymal transition (EndMT). Gram-negative bacteria and their cell wall component lipopolysaccharides (LPSs) are frequently involved in the pathogenesis of AKI. The host recognition of LPS requires a specific receptor, which belongs to the Toll-like receptor (TLR) family of proteins, called TLR4, and two carrier proteins, namely the LPS-binding protein (LBP) and cluster of differentiation 14 (CD14). In particular, LBP is released as a consequence of Gram-negative infection and maximizes the activation of TLR4 signalling. Recent findings regarding the emerging role of LBP in mediating sepsis-induced AKI, and the possible beneficial effects resulting from the removal of this endogenous adaptor protein, will be discussed in this review.
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari 'Aldo Moro', Policlinico, Bari, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Stasi
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari 'Aldo Moro', Policlinico, Bari, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Intini
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari 'Aldo Moro', Policlinico, Bari, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Divella
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari 'Aldo Moro', Policlinico, Bari, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Franzin
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari 'Aldo Moro', Policlinico, Bari, Italy.
authors.forename: Eustacchio
authors.initials: E
authors.lastname: Montemurno
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital and the International Renal Research Institute, Vicenza, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco
authors.affiliation: Department of Clinical Sciences, University of Parma, Parma, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Fiaccadori
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari 'Aldo Moro', Policlinico, Bari, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Pertosa
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari 'Aldo Moro', Policlinico, Bari, Italy.
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari 'Aldo Moro', Policlinico, Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castellano
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018805:Sepsis / Q000150:complications*; D015398:Signal Transduction; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein
keywords: LPS-binding protein; endothelial dysfunction; renal fibrosis; sepsis-induced acute kidney injury; tubular maladaptive response