Abstract
The major role of Hippo signaling is to inhibit their downstream effectors YAP/TAZ for organ size control during development and regeneration (Nat Rev Drug Discov 13(1):63–79, 2014; Dev Cell 19(4):491–505, 2010; Cell 163(4):811–828, 2015). We and others have demonstrated that the genetic disruption of kinases Mst1 and Mst2 (Mst1/2), the core components of Hippo signaling, results in YAP activation and sustained liver growth, thereby leading to an eight- to tenfold increase in liver size within 3 months and occurrence of liver cancer within 5 months (Curr Biol 17(23):2054–2060, 2007; Cancer Cell 16(5):425–438, 2009; Cell 130(6):1120–1133, 2007; Cancer Cell 31(5):669–684 e667, 2017; Nat Commun 6:6239, 2015; Cell Rep 3(5):1663–1677, 2013). XMU-MP-1, an Mst1/2 inhibitor, is able to augment mouse liver and intestinal repair and regeneration in both acute and chronic injury mouse models (Sci Transl Med 8:352ra108, 2016).In addition, YAP-deficient mice show an impaired intestinal regenerative response after DSS treatment or gamma irradiation (Proc Natl Acad Sci U S A 108(49):E1312–1320, 2011; Nature 493(7430):106–110, 2013; Genes Dev 24(21):2383–2388, 2010; J Vis Exp (111), 2010). IBS008738, a TAZ activator, facilitates muscle repair after cardiotoxin-induced muscle injury (Mol Cell Biol. 2014;34(9):1607–21). Deletion of Salvador (Sav) in mouse hearts enhances cardiomyocyte regeneration with reduced fibrosis and recovery of pumping function after myocardial infarction (MI) or resection of mouse cardiac apex (Development 140(23):4683–4690, 2013; Sci Signal 8(375):ra41, 2015; Nature 550(7675):260–264, 2017). This chapter provides a detailed description of procedures and important considerations when performing the protocols for the respective assays used to determine the effects of Hippo signaling on tissue repair and regeneration.
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Acknowledgments
The authors thank Quan Yuan (Xiamen University, China) for critical reading of the protocol of FRG mice model. This work was supported by grants from National Key R&D Program of China 2017YFA0504502 to D.Z. and L.C., the National Natural Science Foundation of China (81790254, 31625010, and U1505224 to D.Z.; U1405225 and 81372617 to L.C.; and 81472229 to L.H.). Lixin Hong and Yuxi Li contributed equally to this work.
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Hong, L., Li, Y., Liu, Q., Chen, Q., Chen, L., Zhou, D. (2019). The Hippo Signaling Pathway in Regenerative Medicine. In: Hergovich, A. (eds) The Hippo Pathway. Methods in Molecular Biology, vol 1893. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8910-2_26
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