| http://purl.uniprot.org/citations/32332915 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32332915 | http://www.w3.org/2000/01/rdf-schema#comment | "Liver dysfunction is strongly associated with poor survival of sepsis patients. Cytosolic lipopolysaccharide (LPS) sensing by Caspase-4/5/11 for pyroptosis activation is a major driver of the development of sepsis. Studies in macrophages and endothelial cells have demonstrated that LPS is inactivated by acyloxyacyl hydrolase (AOAH) and leading to desensitizing Caspase-4/5/11 to LPS. However, little is known about the cytosolic LPS-induced pyroptosis in hepatocytes during sepsis. Heat shock protein 12A (HSPA12A) is a novel member of the HSP70 family. Here, we report that LPS increased HSPA12A nuclear translocation in hepatocytes, while knockout of HSPA12A (Hspa12a-/-) in mice promoted LPS-induced acute liver injury. We also noticed that the LPS-induced Caspase-11 activation and its cleavage of gasdermin D (GSDMD) to produce the membrane pore-forming GSDMDNterm (markers of pyroptosis) were greater in livers of Hspa12a-/- mice compared with its wild type controls. Loss- and gain-of-function studies showed that HSPA12A deficiency promoted, whereas HSPA12A overexpression inhibited, cytosolic LPS accumulation, Caspase-11 activation and GSDMDNterm generation in primary hepatocytes following LPS incubation. Notably, LPS-induced AOAH expression was suppressed by HSPA12A deficiency, whereas AOAH overexpression reversed the HSPA12A deficiency-induced promotion of LPS-evoked and Caspase-11-mediated pyroptosis of hepatocytes. In-depth molecular analysis showed that HSPA12A interacted directly with peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and increased its nuclear translocation, thereby inducing AOAH expression for cytosolic LPS inactivation, which ultimately leading to inhibition of the Caspase-11 mediated pyroptosis of hepatocytes. Taken together, these findings revealed HSPA12A as a novel player against LPS-induced liver injury by inhibiting cytosolic LPS-induced hepatocyte pyroptosis via PGC-1α-mediated AOAH expression. Therefore, targeting hepatocyte HSPA12A represents a viable strategy for the management of liver injury in sepsis patients."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41418-020-0536-x"xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Chen H."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Cao X."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Li C."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Li Y."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Liu J."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Jiang S."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Liu L."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Zhang X."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Ding Z."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Du S."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/author | "Kong Q."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/name | "Cell Death Differ"xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/pages | "2651-2667"xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/title | "HSPA12A attenuates lipopolysaccharide-induced liver injury through inhibiting caspase-11-mediated hepatocyte pyroptosis via PGC-1alpha-dependent acyloxyacyl hydrolase expression."xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://purl.uniprot.org/core/volume | "27"xsd:string |
| http://purl.uniprot.org/citations/32332915 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32332915 |
| http://purl.uniprot.org/citations/32332915 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32332915 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JGG3-mappedCitation-32332915 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32332915 |
| http://purl.uniprot.org/uniprot/#_E0CY92-mappedCitation-32332915 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32332915 |
| http://purl.uniprot.org/uniprot/#_A0A494B917-mappedCitation-32332915 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32332915 |
| http://purl.uniprot.org/uniprot/#_A0A494BAN0-mappedCitation-32332915 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32332915 |