| First Author | Rao S | Year | 2021 |
| Journal | Sci Transl Med | Volume | 13 |
| Issue | 624 | Pages | eabk2267 |
| PubMed ID | 34910547 | Mgi Jnum | J:324545 |
| Mgi Id | MGI:7279056 | Doi | 10.1126/scitranslmed.abk2267 |
| Citation | Rao S, et al. (2021) beta2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development. Sci Transl Med 13(624):eabk2267 |
| abstractText | The prevalence of nonalcoholic steatohepatitis (NASH) and liver cancer is increasing. De novo lipogenesis and fibrosis contribute to disease progression and cancerous transformation. Here, we found that beta2-spectrin (SPTBN1) promotes sterol regulatory element (SRE)-binding protein (SREBP)-stimulated lipogenesis and development of liver cancer in mice fed a high-fat diet (HFD) or a western diet (WD). Either hepatocyte-specific knockout of SPTBN1 or siRNA-mediated therapy protected mice from HFD/WD-induced obesity and fibrosis, lipid accumulation, and tissue damage in the liver. Biochemical analysis suggested that HFD/WD induces SPTBN1 and SREBP1 cleavage by CASPASE-3 and that the cleaved products interact to promote expression of genes with sterol response elements. Analysis of human NASH tissue revealed increased SPTBN1 and CASPASE-3 expression. Thus, our data indicate that SPTBN1 represents a potential target for therapeutic intervention in NASH and liver cancer. |
