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Search progress of pyruvate kinase M2 (PKM2) in organ fibrosis

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Abstract

Fibrosis is characterized by abnormal deposition of the extracellular matrix (ECM), leading to organ structural remodeling and loss of function. The principal cellular effector in fibrosis is activated myofibroblasts, which serve as the main source of matrix proteins. Metabolic reprogramming, transitioning from mitochondrial oxidative phosphorylation to aerobic glycolysis, is widely observed in rapidly dividing cells such as tumor cells and activated myofibroblasts and is increasingly recognized as a fundamental pathogenic basis in organ fibrosis. Targeting metabolism represents a promising strategy to mitigate fibrosis. PKM2, a key enzyme in glycolysis, plays a pivotal role in metabolic reprogramming through allosteric regulation, impacting both metabolic and non-metabolic pathways. Therefore, metabolic reprogramming induced by PKM2 activation is involved in the occurrence and development of fibrosis in various organs. A comprehensive understanding of the role of PKM2 in fibrotic diseases is crucial for seeking new anti-fibrotic therapeutic targets. In this context, we summarize PKM2’s role in glycolysis, mediating the intricate mechanisms underlying fibrosis in multiple organs, and discuss the potential value of PKM2 inhibitors and allosteric activators in future clinical treatments, aiming to identify novel therapeutic targets for proliferative fibrotic diseases.

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Funding

This work was supported by grants from Key R&D Projects of Jiangsu Province (BE2021694).

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  1. Shumei Lv and Mengfei Cao contributed equally to this work.

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  1. Department of Cardiology, Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212000, China

    Shumei Lv, Mengfei Cao, Jie Luo, Kewei Fu & Wei Yuan

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All authors contributed to the review conception and design. Material preparation and document literature collection were performed by J. L, and K. F. The first draft of the manuscript was written by S. L. and M.C. W. Y. edited and revised manuscript. All authors read and approved the final version of the manuscript.

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Lv, S., Cao, M., Luo, J. et al. Search progress of pyruvate kinase M2 (PKM2) in organ fibrosis. Mol Biol Rep 51, 389 (2024). https://doi.org/10.1007/s11033-024-09307-w

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