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Piezo ion channels: long-sought-after mechanosensors mediating hypertension and hypertensive nephropathy

Hypertension Research volume 47, pages 2786–2799 (2024)Cite this article

Abstract

Recent advances in mechanobiology and the discovery of mechanosensitive ion channels have opened a new era of research on hypertension and related diseases. Piezo1 and Piezo2, first reported in 2010, are regarded as bona fide mechanochannels that mediate various biological and pathophysiological phenomena in multiple tissues and organs. For example, Piezo channels have pivotal roles in blood pressure control, triggering shear stress-induced nitric oxide synthesis and vasodilation, regulating baroreflex in the carotid sinus and aorta, and releasing renin from renal juxtaglomerular cells. Herein, we provide an overview of recent literature on the roles of Piezo channels in the pathogenesis of hypertension and related kidney damage, including our experimental data on the involvement of Piezo1 in podocyte injury and that of Piezo2 in renin expression and renal fibrosis in animal models of hypertensive nephropathy.

The mechanosensitive ion channels Piezo1 and Piezo2 play various roles in the pathogenesis of systemic hypertension by acting on vascular endothelial cells, baroreceptors in the carotid artery and aorta, and the juxtaglomerular apparatus. Piezo channels also contribute to hypertensive nephropathy by acting on mesangial cells, podocytes, and perivascular mesenchymal cells.

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Acknowledgements

We thank Dr. Yuki Mochida, Dr. Koji Ochiai, Dr. Satoyuki Ogino, Dr. Kei Yoshikawa, and Dr. Kaori Mikami for their contributions to the experiments described in this review. We also thank Professor Emeritus George Matsumura for the illustration of Fig. 2 and Editage (www.editage.jp) for English language editing.

Funding

This work was supported in part by JSPS KAKENHI Grant Numbers JP17K09736, JP20K08616, JP23K07704, by Japan Agency for Medical Research and Development (18gm5810019h9903), and by the Salt Science Research Foundation, No. 2329.

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  1. Kunitachi Aoyagien Tachikawa Geriatric Health Services Facility, Tokyo, Japan

    Takashi Nagase

  2. Department of Anatomy, Kyorin University School of Medicine, Tokyo, Japan

    Miki Nagase

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Nagase, T., Nagase, M. Piezo ion channels: long-sought-after mechanosensors mediating hypertension and hypertensive nephropathy. Hypertens Res 47, 2786–2799 (2024). https://doi.org/10.1038/s41440-024-01820-6

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