| http://purl.uniprot.org/citations/37586586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37586586 | http://www.w3.org/2000/01/rdf-schema#comment | "Sphingomyelin synthase (SMS)-related protein (SMSr) is a phosphatidylethanolamine phospholipase C (PE-PLC) that is conserved and ubiquitous in mammals. However, its biological function is still not clear. We previously observed that SMS1 deficiency-mediated glucosylceramide accumulation caused nonalcoholic fatty liver diseases (NAFLD), including nonalcoholic steatohepatitis (NASH) and liver fibrosis. Here, first, we evaluated high-fat diet/fructose-induced NAFLD in Smsr KO and WT mice. Second, we evaluated whether SMSr deficiency can reverse SMS1 deficiency-mediated NAFLD, using Sms1/Sms2 double and Sms1/Sms2/Smsr triple KO mice. We found that SMSr/PE-PLC deficiency attenuated high-fat diet/fructose-induced fatty liver and NASH, and attenuated glucosylceramide accumulation-induced NASH, fibrosis, and tumor formation. Further, we found that SMSr/PE-PLC deficiency reduced the expression of many inflammatory cytokines and fibrosis-related factors, and PE supplementation in vitro or in vivo mimicked the condition of SMSr/PE-PLC deficiency. Furthermore, we demonstrated that SMSr/PE-PLC deficiency or PE supplementation effectively prevented membrane-bound β-catenin transfer to the nucleus, thereby preventing tumor-related gene expression. Finally, we observed that patients with NASH had higher SMSr protein levels in the liver, lower plasma PE levels, and lower plasma PE/phosphatidylcholine ratios, and that human plasma PE levels are negatively associated with tumor necrosis factor-α and transforming growth factor β1 levels. In conclusion, SMSr/PE-PLC deficiency causes PE accumulation, which can attenuate fatty liver, NASH, and fibrosis. These results suggest that SMSr/PE-PLC inhibition therapy may mitigate NAFLD."xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jbc.2023.105162"xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/author | "He M."xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/author | "Han X."xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/author | "Li Z."xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/author | "Pan M."xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/author | "Jiang X.C."xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/author | "Chiang Y.P."xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/author | "Jones Q."xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/pages | "105162"xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/title | "Sphingomyelin synthase-related protein SMSr is a phosphatidylethanolamine phospholipase C that promotes nonalcoholic fatty liver disease."xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://purl.uniprot.org/core/volume | "299"xsd:string |
| http://purl.uniprot.org/citations/37586586 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/37586586 |
| http://purl.uniprot.org/citations/37586586 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/37586586 |
| http://purl.uniprot.org/uniprot/#_D3YVS9-mappedCitation-37586586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37586586 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JFH1-mappedCitation-37586586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37586586 |
| http://purl.uniprot.org/uniprot/#_A0A494BA77-mappedCitation-37586586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37586586 |
| http://purl.uniprot.org/uniprot/#_D3YV54-mappedCitation-37586586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37586586 |
| http://purl.uniprot.org/uniprot/#_D6REI9-mappedCitation-37586586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37586586 |
| http://purl.uniprot.org/uniprot/#_E3W996-mappedCitation-37586586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37586586 |
| http://purl.uniprot.org/uniprot/#_Q14AQ4-mappedCitation-37586586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37586586 |
| http://purl.uniprot.org/uniprot/#_Q3UH82-mappedCitation-37586586 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37586586 |