Research Paper Volume 16, Issue 11 pp 9460—9469
High glucose enhances fibrosis in human annulus fibrosus cells by activating mTOR, PKCδ, and NF-κB signaling pathways
- 1 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
- 2 Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
- 3 Spine Center, China Medical University Hospital, Taichung, Taiwan
- 4 Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan
- 5 Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan
- 6 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
- 7 Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
- 8 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
- 9 Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan
- 10 Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
Received: January 19, 2024 Accepted: April 10, 2024 Published: May 29, 2024
https://doi.org/10.18632/aging.205876How to Cite
Copyright: © 2024 Tseng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Low back pain stands as a significant factor in disability, largely resulting from intervertebral disc degeneration (IVDD). High glucose (HG) levels have been implicated in the pathogenesis of IVDD. However, the detailed mechanism of HG in IVDD is largely unknown. Our clinical results revealed that fibrosis markers such as CTGF, Col1a1, ATF4, and EIF2 are highly expressed in advanced-stage IVDD patients. Stimulation of human annulus fibrosus cells (HAFCs) with HG, but not mannitol, promotes fibrosis protein production. Ingenuity Pathway Analysis in the GSE database found that the mTOR, PKCδ, and NF-κB pathways were significantly changed during IVDD. The mTOR, PKCδ, and NF-κB inhibitors or siRNAs all abolished HG-induced fibrosis protein production. In addition, treatment of HAFCs with HG enhances the activation of mTOR, PKCδ, and NF-κB pathways. Thus, HG facilitates fibrosis in IVDD through mTOR, PKCδ, and NF-κB pathways. These results underscore the critical role of HG as a fibrotic factor in the progression of IVDD.