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Shao D, Zhai P, Hu C, et al. Lats2 promotes heart failure by stimulating p53-mediated apoptosis during pressure overload. Sci Rep. 2021;11(1):23469doi: 10.1038/s41598-021-02846-3.
Shao, D., Zhai, P., Hu, C., Mukai, R., Sciarretta, S., Del Re, D., & Sadoshima, J. (2021). Lats2 promotes heart failure by stimulating p53-mediated apoptosis during pressure overload. Scientific reports, 11(1), 23469. https://doi.org/10.1038/s41598-021-02846-3
Shao, Dan, et al. "Lats2 promotes heart failure by stimulating p53-mediated apoptosis during pressure overload." Scientific reports vol. 11,1 (2021): 23469. doi: https://doi.org/10.1038/s41598-021-02846-3
Shao D, Zhai P, Hu C, Mukai R, Sciarretta S, Del Re D, Sadoshima J. Lats2 promotes heart failure by stimulating p53-mediated apoptosis during pressure overload. Sci Rep. 2021 Dec 06;11(1):23469. doi: 10.1038/s41598-021-02846-3. PMID: 34873220; PMCID: PMC8648781.
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Sci Rep. 2021 Dec 06;11(1):23469. doi: 10.1038/s41598-021-02846-3.

Lats2 promotes heart failure by stimulating p53-mediated apoptosis during pressure overload.

Scientific reports

Dan Shao, Peiyong Zhai, Chengchen Hu, Risa Mukai, Sebastiano Sciarretta, Dominic Del Re, Junichi Sadoshima

Affiliations

  1. Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, 185 S Orange Ave, MSB G609, Newark, NJ, 07103, USA.
  2. Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
  3. IRCCS Neuromed, Pozzilli, IS, Italy.
  4. Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, 185 S Orange Ave, MSB G609, Newark, NJ, 07103, USA. [email protected].

PMID: 34873220 PMCID: PMC8648781 DOI: 10.1038/s41598-021-02846-3

Abstract

The Hippo pathway plays a wide variety of roles in response to stress in the heart. Lats2, a component of the Hippo pathway, is phosphorylated by Mst1/2 and, in turn, phosphorylates YAP, causing inactivation of YAP. Lats2 stimulates apoptosis and negatively affects hypertrophy in cardiomyocytes. However, the role of Lats2 during cardiac stress is poorly understood in vivo. Lats2 is activated in the mouse heart in response to transverse aortic constriction (TAC). We used systemic Lats2 +/- mice to elucidate the role of endogenous Lats2. Cardiac hypertrophy and dysfunction induced by 4 weeks of TAC were attenuated in Lats2 +/- mice, and interstitial fibrosis and apoptosis were suppressed. Although TAC upregulated the Bcl-2 family proapoptotic (Bax and Bak) and anti-apoptotic (Bcl-2 and Bcl-xL) molecules in non-transgenic mice, TAC-induced upregulation of Bax and Bak was alleviated and that of Bcl-2 was enhanced in Lats2 +/- mice. TAC upregulated p53, but this upregulation was abolished in Lats2 +/- mice. Lats2-induced increases in apoptosis and decreases in survival in cardiomyocytes were inhibited by Pifithrin-α, a p53 inhibitor, suggesting that Lats2 stimulates apoptosis via a p53-dependent mechanism. In summary, Lats2 is activated by pressure overload, thereby promoting heart failure by stimulating p53-dependent mechanisms of cell death.

© 2021. The Author(s).

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