Abstract
Transcription Factor Pitx2 Promotes Myocardial Regeneration after Ischemic Injury
The Thoracic and Cardiovascular Surgeon, Vol.64(S 01)
45th Annual Meeting of the German Society for Thoracic and Cardiovascular Surgery (DGTHG) - Leipzig, Germany - 2016
01/20/2016
DOI: 10.1055/s-0036-1571557
Abstract
Objectives:
The lack of self-renewal capacity in the mature heart is a major reason for heart failure after myocardial infarction (MI). To repopulate a damaged heart with de novo cardiomyocytes, one promising strategy is to reintroduce mature cardiomyocytes into mitotic cycle. We have previously reported that the mouse Hippo signaling pathway is a major heart-size control pathway during development. Knocking-down of Hippo (Hippo-deficient) activates its downstream effectors (Yap/Taz) and promotes juvenile and adult myocardial regeneration after MI. Here, we aimed at identifying new partners of the Hippo -kinase-cascade in myocardial regeneration.
Methods and Results:
While Co-IP assays indicated a direct interaction between Pitx2 and YAP, knocking-down of Pitx2 in Hippo-deficient hearts resulted in severe scarring after MI, implicating a requirement of Pitx2 for the regeneration of Hippo-deficient hearts. We found that Pitx2 expression is induced in injured ventricular myocardium, and is required in neonatal cardiac regeneration. Immunostaining, ChIP-seq and RNA-seq studies showed that Pitx2 positively regulates cell-proliferation and the expression of antioxidant scavenger genes. In addition, increased levels of reactive oxygen species (ROS) in Pitx2 knockdown hearts are partially responsible for impeding neonatal myocardial regeneration. Further studies revealed that overexpression of Pitx2 in adult cardiomyocytes is sufficient to promote the restoration of myocardial structure and function after MI.
Conclusions:
Together these evidences revealed a new role of Pitx2 as a partner of Hippo signaling in ventricular myocardium and showed the potential of Pitx2 as a therapeutic target in future cardiac regenerative medicine.
Details
- Title: Subtitle
- Transcription Factor Pitx2 Promotes Myocardial Regeneration after Ischemic Injury
- Creators
- P. C. Kahr - Baylor College of MedicineG. Tao - Baylor College of MedicineY. Morikawa - Texas Heart Institute, Cardiomyocyte Renewal Lab, Houston, United StatesM. Zhang - Baylor College of MedicineL. Li - Baylor College of MedicineZ. Sun - University of IowaB. A. Amendt - University of IowaJ. F. Martin - Texas Heart Institute, Cardiomyocyte Renewal Lab, Houston, United States
- Resource Type
- Abstract
- Publication Details
- The Thoracic and Cardiovascular Surgeon, Vol.64(S 01)
- Conference
- 45th Annual Meeting of the German Society for Thoracic and Cardiovascular Surgery (DGTHG) - Leipzig, Germany - 2016
- DOI
- 10.1055/s-0036-1571557
- ISSN
- 0171-6425
- eISSN
- 1439-1902
- Language
- English
- Date published
- 01/20/2016
- Academic Unit
- Orthodontics; Iowa Technology Institute; Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984288753502771
Metrics
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