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REVIEW article

Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1476699
This article is part of the Research Topic The Mechanisms of Fibrotic Disorders and Pharmacological Therapies View all 8 articles

New insights into SUMOylation and NEDDylation in fibrosis

Provisionally accepted
Jin Han Jin Han 1Jun Wu Jun Wu 2Wen-Tao Kou Wen-Tao Kou 1Li-Na Xie Li-Na Xie 1Ya-Li Tang Ya-Li Tang 1Da-Long Zhi Da-Long Zhi 1Ping Li Ping Li 3Dan-Qian Chen Dan-Qian Chen 1*
  • 1 Northwest University, Xi'an, China
  • 2 Shandong College of Traditional Chinese Medicine, Yantai, Shandong Province, China
  • 3 China-Japan Friendship Hospital, Beijing, Beijing Municipality, China

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

    Fibrosis is the outcome of abnormal tissue repair process that the normal tissue is replaced by scar tissue, and causes persistent tissue damage and cellular injury. During fibrosis process, many cytokines and chemokines is involved, and their activity is controlled by post-translational modifications, especially SUMOylation and NEDDylation. Both SUMOylation and NEDDylation have the three-step process that consists of activation, conjugation and ligation, and three kinds of enzymes are involved, including E1 activating enzyme, E2 conjugating enzyme and E3 ligase enzyme. SUMOylation participate organ fibrosis through modulating FXR, PML, TGF-β receptor I, Sirt3, HIF-1α and Sirt1, and NEDDylation influences organ fibrosis through regulating cullin3, NIK, SRSF3 and UBE2M.Further investigations exhibit the therapeutic potential of SUMOylation /NEDDylation activators and inhibitors against organ fibrosis, especially ginkgolic acid in SUMOylation and MLN4924 in NEDDylation. These results demonstrate the therapeutic effect of SUMOylation and NEDDylation against organ fibrosis, and highlight their activators and inhibitors as potential candidates. In the future, the deep investigation of SUMOylation and NEDDylation are urgent to identify novel substrates against organ fibrosis, and the clinical investigation are needed to determine the therapeutic effect of their activators and inhibitors to benefit patients. The information in this review highlights that SUMOylation and NEDDylation functions as the potential therapeutic target for organ fibrosis.

    Keywords: Sumoylation, Neddylation, Fibrosis, Ginkgolic acid, MLN4924

    Received: 06 Aug 2024; Accepted: 12 Nov 2024.

    Copyright: © 2024 Han, Wu, Kou, Xie, Tang, Zhi, Li and Chen. 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

    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.