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

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, Elizabeth J. Cartwright and Delvac Oceandy ()
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Bayu Lestari: Manchester Academic Health Science Centre
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
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

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-56531-4

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