文献类型：期刊文献

英文题名：Yap signalling regulates ductular reactions in mice with CRISPR/Cas9-induced glycogen storage disease type Ia

作者：Xie, Yixia[1,2];Hu, Baowei[1];Gao, Yue[1];Tang, Yaxin[1];Chen, Guohe[1];Shen, Jiayuan[3];Jiang, Zhikai[4];Jiang, He[5];Han, Jiwei[1];Yan, Junyan[1];Jin, Lifang[1,2]

机构：[1]Shaoxing Univ, Sch Life Sci, Shaoxing 312000, Zhejiang, Peoples R China;[2]Zhejiang Sci Tech Univ, Shaoxing Acad Biomed, Shaoxing 312000, Zhejiang, Peoples R China;[3]Shaoxing Univ, Dept Pathol, Affiliated Hosp, Shaoxing, Zhejiang, Peoples R China;[4]Wenzhou Med Univ, Clin Med Coll 2, Wenzhou, Zhejiang, Peoples R China;[5]Chinese Med Univ, Clin Med Sch Zhejiang 1, Hangzhou, Zhejiang, Peoples R China

年份：0

外文期刊名：ANIMAL CELLS AND SYSTEMS

收录：SCI-EXPANDED(收录号：WOS:000879635800001)、、Scopus(收录号：2-s2.0-85141613976)、WOS

基金：This work was supported by research grants from Scientific Research Platform of Molecular Pathology Detection Center for Tumor Genes, Shaoxing University. The project was also supported by Open Fund of Shaoxing Academy of Biomedicine of Zhejiang Sci-Tech University (NO. SXAB202015).

语种：英文

外文关键词：GSD-Ia; ductular reactions; yap; CRISPR-Cas9; G6pc

外文摘要：Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in the glucose-6-phosphatase (G6Pase, G6pc) enzyme, which catalyses the final step of gluconeogenesis and glycogenolysis. Accumulation of G6pc can lead to an increase in glycogen and development of fatty liver. Ductular reactions refer to the proliferation of cholangiocytes and hepatic progenitors, which worsen fatty liver progress. To date, however, ductular reactions in GSD-Ia remain poorly understood. Here, we studied the development and potential underlying mechanism of ductular reactions in GSD-Ia in mice. We first generated GSD-Ia mice using CRISPR/Cas9 to target the exon 3 region of the G6pc gene. The typical GSD-Ia phenotype in G6pc(-/-) mice was then analysed using biochemical and histological assays. Ductular reactions in G6pc(-/-) mice were tested based on the expression of cholangiocytic markers cytokeratin 19 (CK19) and epithelial cell adhesion molecule (EpCAM). Yes-associated protein 1 (Yap) signalling activity was measured using western blot (WB) analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Verteporfin was administered to the G6pc(-/-) mice to inhibit Yap signalling. The CRISPR/Cas9 system efficiently generated G6pc(-/-) mice, which exhibited typical GSD-Ia characteristics, including retarded growth, hypoglycaemia, and fatty liver disease. In addition, CK19- and EpCAM-positive cells as well as Yap signalling activity were increased in the livers of G6pc(-/-) mice. However, verteporfin treatment ameliorated ductular reactions and decreased Yap signalling activity. This study not only improves our understanding of GSD-Ia pathophysiology, but also highlights the potential of novel therapeutic approaches for GSD-Ia such as drug targeting of ductular reactions.