| Literature DB >> 34910547 |
Shuyun Rao1,2, Xiaochun Yang1,3, Kazufumi Ohshiro1, Sobia Zaidi1,3, Zhanhuai Wang2,4, Kirti Shetty5, Xiyan Xiang1,3, Md Imtaiyaz Hassan6, Taj Mohammad6, Patricia S Latham2,7, Bao-Ngoc Nguyen2, Linda Wong8,9, Herbert Yu10, Yousef Al-Abed1, Bibhuti Mishra1,11, Michele Vacca12, Gareth Guenigault13, Michael E D Allison14, Antonio Vidal-Puig12,15,16, Jihane N Benhammou17, Marcus Alvarez18, Päivi Pajukanta18,19, Joseph R Pisegna20, Lopa Mishra1,2,3.
Abstract
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 β2-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.Entities:
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Year: 2021 PMID： 34910547 PMCID： PMC8941321 DOI： 10.1126/scitranslmed.abk2267
Source DB: PubMed Journal: Sci Transl Med ISSN： 1946-6234 Impact factor: 17.956