| http://purl.uniprot.org/citations/37478565 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37478565 | http://www.w3.org/2000/01/rdf-schema#comment | "Obese patients usually have hyperleptinemia and are prone to develop liver fibrosis. Leptin is intimately linked to liver fibrogenesis, a multi-receptor-driven disease. Gα-Interacting Vesicle-associated protein (GIV) functions as a multimodular signal transducer and a guanine nucleotide exchange factor for Gi controling key signalings downstream of diverse receptors. This study aimed to examine the roles of GIV in leptin-caused liver fibrosis and employed the culture-activated hepatic stellate cells (HSCs) and leptin-deficient mice, respectively. Results indicated that leptin upregulated GIV expression in HSCs. GIV was involved in leptin-induced HSC activation and liver fibrosis. GIV mediated leptin regulation of TIMP1, MMP9, PDGFβ receptor and TGFβ receptor and was required for leptin stimulating the pathways of Erk1/2, Akt1, and Smad3. GIV was also a mediator for leptin-regulation of Cyclin D1 and Caspase-3 activity but GIV reduced Caspase-3 level independently of leptin in vivo. Erk1/2 signaling, Egr1 and c-Jun were associated with the effect of leptin on GIV expression in HSCs. Leptin-induced Erk1/2 signaling increased Egr1 and p-c-Jun levels and promoted their binding to GIV promoter at the sites between -190 bp and -180 bp and between -382 bp and -376 bp, respectively. Egr1 knockdown lessened leptin-upregulation of GIV in vitro and in vivo. In human cirrhotic livers, the increase in GIV protein level parallelled with the elevated p-Erk1/2 and Egr1 levels in HSCs. In summary, the unusual signal transducer GIV was identified as an important mediator in leptin-induced liver fibrosis. GIV may have significant implications in liver fibrosis progression of obese patients with hyperleptinaemia."xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bbadis.2023.166797"xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/author | "Lu S."xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/author | "Jia X."xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/author | "Guan W."xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/author | "Zhou Y."xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/author | "Xu F."xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/author | "Jie H."xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/name | "Biochim Biophys Acta Mol Basis Dis"xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/pages | "166797"xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/title | "An unusual signal transducer GIV/Girdin engages in the roles of adipocyte-derived hormone leptin in liver fibrosis."xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://purl.uniprot.org/core/volume | "1869"xsd:string |
| http://purl.uniprot.org/citations/37478565 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/37478565 |
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