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

        Yixia Xie,Baowei Hu,Yue Gao,Yaxin Tang,Guohe Chen,Jiayuan Shen,Zhikai Jiang,He Jiang,Jiwei Han,Junyan Yan,Lifang Jin 한국통합생물학회 2022 Animal cells and systems Vol.26 No.6

        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.

      • VPIT : An Improved Range-Free Localization Algorithm Using Voronoi Diagrams for Wireless Sensor Networks

        Xingming Sun,Yachao Hu,Baowei Wang,Jian Zhang,Tao Li 보안공학연구지원센터 2015 International Journal of Multimedia and Ubiquitous Vol.10 No.8

        Localization systems have been identified as key issues in the development and operation of wireless sensor networks. The global positioning system (GPS) solves the problem about localization, but it is not suitable for wireless sensor networks. Due to range-free localization approaches requiring low equipped hardware and easy to implement, it is widely used in WSNs localization system. When the node communication radius increases, the accuracy of area-based localization is reduced. It is important to improve the localization accuracy in this situation. In this paper, to improve the accuracy of the node localization, we propose a new range-free localization using Voronoi diagrams based approximate point-in-triangulation test (APIT) algorithm. We compare our algorithm with APIT. Simulation results show that the VPIT improved the precision of localization by narrowing the node's geometry region.

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