Macrophage migration inhibitory factor (MIF) promotes intervertebral disc degeneration through the NF-κB pathway, and the MIF inhibitor CPSI-1306 alleviates intervertebral disc degeneration in a mouse model.

Abstract

Lumbar intervertebral disc degeneration(IDD) is a prevalent inflammatory disease caused by many proinflammatory factors, such as TNF and IL-1β. Migration inhibitory factor (MIF) is an upstream inflammatory factor widely expressed in vivo that is associated with a variety of inflammatory diseases or malignant tumors and has potential therapeutic value in many diseases. We explored the role of MIF in intervertebral disc degeneration by regulating the content of exogenous MIF or the expression of MIF in cells. Upon inducing degeneration of nucleus pulposus (NP) cells with IL-1β, we found that the increase in intracellular and exogenous MIF promoted the catabolism induced by proinflammatory factors in NP cells, while silencing of the MIF gene alleviated the degeneration to some extent. In a mouse model, the intervertebral disc degeneration of MIF-KO mice was significantly less than that of wild-type mice. To explore the treatment of intervertebral disc degeneration, we selected the small-molecular MIF inhibitor CPSI-1306. CPSI-1306 had a therapeutic effect on intervertebral disc degeneration in the mouse model. In summary, we believe that MIF plays an important role in intervertebral disc degeneration and is a potential therapeutic target for the treatment of intervertebral disc degeneration.

• Authors: Yejin Zhang, Lin Zheng, Jiawei Fang, Kainan Ni, Xingyu Hu, Lin Ye, Hehuan Lai, Tao Yang, Zhenzhong Chen, Dengwei He
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 37 Issue 12 Pg. e23303 (12 2023) ISSN: 1530-6860 [Electronic] United States
• PMID: 37983963 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 Federation of American Societies for Experimental Biology.

Chemical References

• NF-kappa B
• CPSI-1306
• Macrophage Migration-Inhibitory Factors

Topics

• Mice
• Animals
• NF-kappa B (metabolism)
• Intervertebral Disc Degeneration (metabolism)
• Signal Transduction (physiology)
• Macrophage Migration-Inhibitory Factors (metabolism)
• Nucleus Pulposus (metabolism)
• Intervertebral Disc (metabolism)