Molecular insights into P2X signalling cascades in acute kidney injury.

Acute kidney injury (AKI) is a critical health issue with high mortality and morbidity rates in hospitalized individuals. The complex pathophysiology and underlying health conditions further complicate AKI management. Growing evidence suggests the pivotal role of ion channels in AKI progression, through promoting tubular cell death and altering immune cell functions. Among these channels, P2X purinergic receptors emerge as key players in AKI pathophysiology. P2X receptors gated by adenosine triphosphate (ATP), exhibit increased extracellular levels of ATP during AKI episodes. More importantly, certain P2X receptor subtypes upon activation exacerbate the situation by promoting the release of extracellular ATP. While therapeutic investigations have primarily focused on P2X4 and P2X7 subtypes in the context of AKI, while understanding about other subtypes still remains limited. Whilst some P2X antagonists show promising results against different types of kidney diseases, their role in managing AKI remains unexplored. Henceforth, understanding the intricate interplay between P2X receptors and AKI is crucial for developing targeted interventions. This review elucidates the functional alterations of all P2X receptors during normal kidney function and AKI, offering insights into their involvement in AKI. Notably, we have highlighted the current knowledge of P2X receptor antagonists and the possibilities to use them against AKI in the future. Furthermore, the review delves into the pathways influenced by activated P2X receptors during AKI, presenting potential targets for future therapeutic interventions against this critical condition. Similar content being viewed by others Data availability No datasets were generated or analysed during the current study.

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ABG sincerely acknowledges the financial support provided by the Birla Institute of Technology and Science-Pilani, Pilani, for carrying out this work. Funding Not applicable. Author information Authors and Affiliations Contributions Swati Mishra: conducted literature research and wrote the manuscript. Vishwadeep Shelke: conceptualized, conducted literature research and co-wrote the manuscript. Neha Dagar: conducted literature research and co-wrote the manuscript. Maciej Lech: participated in designing the manuscript, edited, and prepared it for submission. Anil Bhanudas Gaikwad: conceptualized, designed and drafted the manuscript. All authors read and approved the final manuscript. Corresponding author Ethics declarations Ethical approval Not applicable. Clinical trial number Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Mishra, S., Shelke, V., Dagar, N. et al. Molecular insights into P2X signalling cascades in acute kidney injury. Purinergic Signalling 20, 477–486 (2024). https://doi.org/10.1007/s11302-024-09987-w Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11302-024-09987-w