The Hippo Signaling Pathway in Regenerative Medicine.
Methods Mol Biol
; 1893: 353-370, 2019.
Article
in En
| MEDLINE
| ID: mdl-30565146
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 66239, 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 8352ra108, 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Signal Transduction
/
Protein Serine-Threonine Kinases
/
Regenerative Medicine
Type of study:
Etiology_studies
/
Guideline
Limits:
Animals
Language:
En
Journal:
Methods Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2019
Type:
Article
Affiliation country:
China