TY - JOUR
T1 - Emerging role of Lipopolysaccharide binding protein in sepsis-induced acute kidney injury
AU - Stasi, Alessandra
AU - Intini, Angelica
AU - Divella, Chiara
AU - Franzin, Rossana
AU - Montemurno, Eustacchio
AU - Grandaliano, Giuseppe
AU - Ronco, Claudio
AU - Fiaccadori, Enrico
AU - Pertosa, Giovanni Battista
AU - Gesualdo, Loreto
AU - Castellano, Giuseppe
PY - 2017
Y1 - 2017
N2 - 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 themajor 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.
AB - 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 themajor 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.
KW - LPS-binding protein
KW - endothelial dysfunction
KW - renal fibrosis
KW - sepsis-induced acute kidney injury
KW - tubular maladaptive response
KW - LPS-binding protein
KW - endothelial dysfunction
KW - renal fibrosis
KW - sepsis-induced acute kidney injury
KW - tubular maladaptive response
UR - http://hdl.handle.net/10807/171162
U2 - 10.1093/ndt/gfw250
DO - 10.1093/ndt/gfw250
M3 - Article
SN - 0931-0509
VL - 32
SP - 24
EP - 31
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
ER -