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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1539317
This article is part of the Research Topic Investigating Splicing Event as Therapeutic Targets in Inflammatory disease View all 4 articles

Interaction with IGF1 overrides ANXA2-mediated anti-inflammatory functions of IGFBP5 in vivo

Provisionally accepted
Yi-jin Wu Yi-jin Wu 1,2*Yan Fan Yan Fan 3Kai Guo Kai Guo 3Xia-Qing Zhou Xia-Qing Zhou 3Abulizi Abulaiti Abulizi Abulaiti 4Opeyemi Joshua Olatunji Opeyemi Joshua Olatunji 5Cong-Lan Ji Cong-Lan Ji 6Jian Zuo Jian Zuo 3
  • 1 Second Affiliated Hospital of Wannan Medical College, Wuhu, China
  • 2 Sichuan University, Chengdu, Sichuan Province, China
  • 3 First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China
  • 4 Uyghur Medical Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, China
  • 5 Mohammed VI Polytechnic University, Ben Guerir, Morocco
  • 6 Anhui University of Chinese Medicine, Hefei, Anhui Province, China

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

    IGFBP5 is a differentially expressed gene (DEG) between M1 and M2 macrophages.This study explained why it causes opposite effects in different circumstances. Gene expression profiles of various cell subsets were compared by mining a public database.THP-1 cells were treated by siRNAs, recombinant IGFBP5, lipopolysaccharide (LPS), picropodophyllin, IGF1 or the combinations. Clinical implication of IGFBP5 changes was investigated using rheumatoid arthritis (RA) and acute lung injury (ALI) models.IGFBP5-bound and differential proteins were identified by Liquid Chromatography Mass Spectrometry method. IGFBP5 situated in the center of a network constructed by the DEGs of M0 and M1/2 macrophages. Its expression negatively correlated to inflammation in vitro. When IGFBP5 was silenced, monocytes released more IL-1β and IL-6. NF-κB downstream proteins were overexpressed. IGFBP5 interacted with ANXA2 directly. In ANXA2-silenced cells, it showed no anti-inflammatory effect.Monocytes of adjuvant-induced arthritis rats and RA patients expressed less IGFBP5 than normal controls, but its blood levels increased significantly. Adipocytes secreted large amounts of IGFBP5. This secretion was reinforced by the above sera. IGFBP5 decreased in ALI mice's blood, while its supplement exacerbated inflammation. By binding to IGF1, IGFBP5 prevented its interaction with IGF1R. An IGF1R inhibitor picropodophyllin antagonized functions of IGF1/IGF1R too, but didn't reinforce the effects of IGFBP5. In short, IGFBP5 eases inflammation by interacting with ANXA2, an activator of NF-κB; as an antagonist of IGF1/IGF1R, IGFBP5 may disrupt immune homeostasis in vivo, due to impairment of the latter's anti-inflammatory functions; excessive IGFBP from adipocytes would be a pathogenic factor in certain diseases.

    Keywords: NF-κB, IGF1/IGF1R, AnxA2, Rheumatoid arthritis, Acute Lung Injury

    Received: 04 Dec 2024; Accepted: 24 Dec 2024.

    Copyright: © 2024 Wu, Fan, Guo, Zhou, Abulaiti, Olatunji, Ji and Zuo. 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: Yi-jin Wu, Second Affiliated Hospital of Wannan Medical College, Wuhu, 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.