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REVIEW article

Front. Pharmacol.
Sec. Renal Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1376252
This article is part of the Research Topic Acute Kidney Injury: From Pathology to Phytotherapy View all 14 articles

Targeting pyruvate kinase M2 for the treatment of kidney disease

Provisionally accepted
Dan-Qian Chen Dan-Qian Chen 1*Jin Han Jin Han 1Hui Liu Hui Liu 1Kai Feng Kai Feng 1Ping Li Ping Li 2*
  • 1 Northwest University, Xi'an, China
  • 2 China-Japan Friendship Hospital, Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    Pyruvate kinase M2 (PKM2), a rate limiting enzyme in glycolysis, is a cellular regulator that has received extensive attention and regards as a metabolic regulator of cellular metabolism and energy. Kidney is a highly metabolically active organ, and glycolysis is the important energy resource for kidney. The accumulated evidences indicates that the enzymatic activity of PKM2 is disturbed in kidney disease progression and treatment, especially diabetic kidney disease and acute kidney injury. Modulating PKM2 post-translational modification determines its enzymatic activity and nuclear translocation that serves as an important interventional approach to regulate PKM2. Emerging evidences show that PKM2 and its post-translational modification participate in kidney disease progression and treatment through modulating metabolism regulation, podocyte injury, fibroblast activation and proliferation, macrophage polarization, and T cell regulation. Interestingly, PKM2 activators (TEPP-46, DASA-58, mitapivat and TP-1454) and PKM2 inhibitors (shikonin, alkannin, compound 3k and compound 3h) have exhibited potential therapeutic property in kidney disease, which indicates the pleiotropic effects of PKM2 in kidney. In the future, the deep investigation of PKM2 pleiotropic effects in kidney is urgently needed to determine the therapeutic effect of PKM2 activator/inhibitor to benefit patients. The information in this review highlights that PKM2 functions as a potential biomarker and therapeutic target for kidney diseases.

    Keywords: pyruvate kinase M2, Diabetic kidney disease, Acute Kidney Injury, post-translational modification, Glycolysis

    Received: 25 Jan 2024; Accepted: 05 Apr 2024.

    Copyright: © 2024 Chen, Han, Liu, Feng and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Dan-Qian Chen, Northwest University, Xi'an, China
    Ping Li, China-Japan Friendship Hospital, Beijing, 100029, Beijing Municipality, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.