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Expression of foetal gene Pontin is essential in protecting heart against pathological remodelling and cardiomyopathy

Author

Listed:
  • Bayu Lestari

    (Manchester Academic Health Science Centre
    Universitas Brawijaya)

  • Ardiansah Bayu Nugroho

    (Manchester Academic Health Science Centre)

  • Thuy Anh Bui

    (Manchester Academic Health Science Centre)

  • Binh Nguyen

    (Manchester Academic Health Science Centre)

  • Nicholas Stafford

    (Manchester Academic Health Science Centre
    Manchester Academic Health Science Centre)

  • Sukhpal Prehar

    (Manchester Academic Health Science Centre)

  • Min Zi

    (Manchester Academic Health Science Centre)

  • Ryan Potter

    (Manchester Academic Health Science Centre)

  • Efta Triastuti

    (Manchester Academic Health Science Centre)

  • Florence M. Baudoin

    (Manchester Academic Health Science Centre)

  • Alicia D’Souza

    (Imperial College)

  • Xin Wang

    (Manchester Academic Health Science Centre)

  • Elizabeth J. Cartwright

    (Manchester Academic Health Science Centre)

  • Delvac Oceandy

    (Manchester Academic Health Science Centre)

Abstract

Cardiac remodelling is a key process in the development of heart failure. Reactivation of foetal cardiac genes is often associated with cardiac remodelling. Here we study the role of Pontin (Ruvbl1), which is highly expressed in embryonic hearts, in mediating adverse remodelling in adult mouse hearts. We observe that Pontin deficiency in cardiomyocytes leads to induced apoptosis, increased hypertrophy and fibrosis, whereas Pontin overexpression improves survival, increases proliferation and reduces the hypertrophic response. Moreover, RNAseq analysis show that genes involved in cell cycle regulation, cell proliferation and cell survival/apoptosis are differentially expressed in Pontin knockout. Specifically, we detect changes in the expression of Hippo pathway components in the Pontin knockout mice. Using a cellular model we show that Pontin induces YAP activity, YAP nuclear translocation, and transcriptional activity. Our findings identify Pontin as a modulator of adverse cardiac remodelling, possibly via regulation of the Hippo pathway. This study may lead to the development of a new approach to control cardiac remodelling by targeting Pontin.

Suggested Citation

  • Bayu Lestari & Ardiansah Bayu Nugroho & Thuy Anh Bui & Binh Nguyen & Nicholas Stafford & Sukhpal Prehar & Min Zi & Ryan Potter & Efta Triastuti & Florence M. Baudoin & Alicia D’Souza & Xin Wang & Eliz, 2025. "Expression of foetal gene Pontin is essential in protecting heart against pathological remodelling and cardiomyopathy," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56531-4
    DOI: 10.1038/s41467-025-56531-4
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    References listed on IDEAS

    as
    1. Ruisheng Song & Wei Peng & Yan Zhang & Fengxiang Lv & Hong-Kun Wu & Jiaojiao Guo & Yongxing Cao & Yanbin Pi & Xin Zhang & Li Jin & Mao Zhang & Peng Jiang & Fenghua Liu & Shaoshuai Meng & Xiuqin Zhang , 2013. "Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders," Nature, Nature, vol. 494(7437), pages 375-379, February.
    2. John P. Leach & Todd Heallen & Min Zhang & Mahdis Rahmani & Yuka Morikawa & Matthew C. Hill & Ana Segura & James T. Willerson & James F. Martin, 2017. "Hippo pathway deficiency reverses systolic heart failure after infarction," Nature, Nature, vol. 550(7675), pages 260-264, October.
    3. Young Suk Yu & Hijai R. Shin & Dongha Kim & Seon Ah Baek & Seon Ah Choi & Hyejin Ahn & Amen Shamim & Jeonghwan Kim & Ik Soo Kim & Kyeong Kyu Kim & Kyoung-Jae Won & Sung Hee Baek, 2020. "Pontin arginine methylation by CARM1 is crucial for epigenetic regulation of autophagy," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    4. Kyungjin Boo & Jinhyuk Bhin & Yoon Jeon & Joomyung Kim & Hi-Jai R. Shin & Jong-Eun Park & Kyeongkyu Kim & Chang Rok Kim & Hyonchol Jang & In-Hoo Kim & V. Narry Kim & Daehee Hwang & Ho Lee & Sung Hee B, 2015. "Pontin functions as an essential coactivator for Oct4-dependent lincRNA expression in mouse embryonic stem cells," Nature Communications, Nature, vol. 6(1), pages 1-16, November.
    5. Dan Shao & Peiyong Zhai & Dominic P. Del Re & Sebastiano Sciarretta & Norikazu Yabuta & Hiroshi Nojima & Dae-Sik Lim & Duojia Pan & Junichi Sadoshima, 2014. "A functional interaction between Hippo-YAP signalling and FoxO1 mediates the oxidative stress response," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
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