Study on the Regulatory Mechanism of Inhibiting miR-153-3p to Delay Intervertebral Disc Degeneration via Nrf2 Regulation

Shan YU; Lin XIAO; Dongping GONG; Loufeng LIANG; Xiayi XU; Huaxin LIANG; Shihai XIAO

doi:10.12259/j.issn.2095-610X.S20250503

Volume 46 Issue 5

May 2025

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Shan YU, Lin XIAO, Dongping GONG, Loufeng LIANG, Xiayi XU, Huaxin LIANG, Shihai XIAO. Study on the Regulatory Mechanism of Inhibiting miR-153-3p to Delay Intervertebral Disc Degeneration via Nrf2 Regulation[J]. Journal of Kunming Medical University, 2025, 46(5): 21-29. doi: 10.12259/j.issn.2095-610X.S20250503

Citation:

Shan YU, Lin XIAO, Dongping GONG, Loufeng LIANG, Xiayi XU, Huaxin LIANG, Shihai XIAO. Study on the Regulatory Mechanism of Inhibiting miR-153-3p to Delay Intervertebral Disc Degeneration via Nrf2 Regulation[J]. Journal of Kunming Medical University, 2025, 46(5): 21-29. doi: 10.12259/j.issn.2095-610X.S20250503

Citation:

Shan YU, Lin XIAO, Dongping GONG, Loufeng LIANG, Xiayi XU, Huaxin LIANG, Shihai XIAO. Study on the Regulatory Mechanism of Inhibiting miR-153-3p to Delay Intervertebral Disc Degeneration via Nrf2 Regulation[J]. Journal of Kunming Medical University, 2025, 46(5): 21-29. doi: 10.12259/j.issn.2095-610X.S20250503

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Study on the Regulatory Mechanism of Inhibiting miR-153-3p to Delay Intervertebral Disc Degeneration via Nrf2 Regulation

doi: 10.12259/j.issn.2095-610X.S20250503

1.
Department of Pain Management，International Zhuang Medicine Hospital Affiliated to Guangxi University of Traditional Chinese Medicine，Nanning Guangxi 530201
2.
Faculty of Zhuang Clinical Medicine of Guangxi University of Chinese Medicine , Nanning Guangxi 530200, China

Received Date: 2024-04-02
Available Online: 2024-11-23
Publish Date: 2025-05-30

Abstract

Abstract

Objective To investigate the correlation mechanism between miR-153-3p and Nrf2 expression in human nucleus pulposus cells and intervertebral disc degeneration （IDD）. Methods The oxidative damage model of nucleus pulposus cells was duplicated induced by H₂O₂. MiR-153-3p inhibitor-NC, si-NRF2-NC, miR-153-3p inhibitor, and si-NRF2 were transfected into nucleus pulposus cells according to the grouping require. The transfection efficiency was detected by RT-qPCR and Western blot. The cell viability was determined by the CCK-8 assay, when the intracellular reactive oxygen species （ROS） levels and the ratio of mitochondrial membrane potential decline were measured by flow cytometry, RT-qPCR was used to detect the expression levels of Nrf2, MMP-3, Col II, PINK1, Parkin, P62, and p38 MAPK. And dual luciferase reporter assay was used to measure luciferase activity. Results （1） HNPCs treated with H₂O₂ showed a decrease in HNPCs cell viability, a reduction in mitochondrial membrane potential, an increase in ROS levels, and a decrease in Col II expression （P < 0.05）. And the expression of MMP-3, P62, and p38 MAPK increased, while the expression of PINK1 and Parkin decreased. There was no significant change in Nrf2（P > 0.05）. （2） Inhibition of miR-153-3p expression in nucleus pulposus cells treated with H₂O₂ led to increased cell viability, elevated mitochondrial membrane potential, reduced ROS levels, and enhanced Col-II expression, accompanied by decreased expression of MMP-3, P62, and p38 MAPK, while simultaneously increasing the expression of PINK1, Parkin, and Nrf2 （P < 0.05）. （3） When miR-153-3p expression was inhibited and Nrf2 expression was silenced in nucleus pulposus cells treated with H₂O₂, a notable decline in cell viability and mitochondrial membrane potential was observed, along with a marked increase in ROS levels. Additionally, Col-II expression decreased, whereas the expression of MMP-3, P62, and p38 MAPK increased. However, the expression of Nrf2, PINK1, and Parkin decreased （P < 0.05）. （4） Dual-luciferase assay analysis revealed binding sites and a binding relationship between miR-153-3p and Nrf2, indicating a negative correlation between miR-153-3p and Nrf2 （P < 0.05）. Conclusion Inhibition of miR-153-3p expression can alleviate H₂O₂ induced degeneration and fibrosis of nucleus pulposus cells, activate autophagy of damaged nucleus pulposus cells, and delay apoptosis of nucleus pulposus cells. This effect is related to the PINK1/Parkin pathway and p38 MAPK inflammatory response pathway regulated by Nrf2.
- Intervertebral disc degeneration,
- Human nucleus pulposus cells,
- miR-153-3p,
- Nrf2

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