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Int J Biol Sci 2024; 20(2):701-717. doi:10.7150/ijbs.90186 This issue Cite

Research Paper

Selective Autophagy Receptor NBR1 Retards Nucleus Pulposus Cell Senescence by Directing the Clearance of SRBD1

Honghai Song^1,2,*, Yutao Zhu^1,2,*, Chuan Hu^1,2,*, Qianyu Liu³, Yang Jin^1,2, Pan Tang^1,6, Jiechao Xia^1,2, Dingqi Xie^1,2, Sicheng Jiang^1,2, Geliang Yao^4,5, Zhili Liu^4,5,✉, Zhijun Hu^1,2,✉

1. Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou 310016, China.
2. Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, China.
3. Ministry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
4. Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
5. Institute of Spine and Spinal Cord, Nanchang University, Nanchang 330006, China.
6. Department of Orthopaedics, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou 313000, China.
^* These authors contributed equally to this work.

✉ Corresponding authors: Zhili Liu, Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University; Institute of Spine and Spinal Cord, Nanchang University, Nanchang 330006, China; Zhijun Hu, Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, China. Email: zhili-liuedu.cn (ZL); hzjspineedu.cn (ZH). More

Abstract

Intervertebral disc degeneration (IDD) is a prevalent degenerative disorder that closely linked to aging. Numerous studies have indicated the crucial involvement of autophagy in the development of IDD. However, the non-selective nature of autophagy substrates poses great limitations on the application of autophagy-related medications. This study aims to enhance our comprehension of autophagy in the development of IDD and investigate a novel therapeutic approach from the perspective of selective autophagy receptor NBR1. Proteomics and immunoprecipitation and mass spectrometry analysis, combined with in vivo and in vitro experimental verification were performed. NBR1 is found to be reduced in IDD, and NBR1 retards cellular senescence and senescence-associated secretory phenotype (SASP) of nucleus pulposus cells (NPCs), primarily through its autophagy-dependent function. Mechanistically, NBR1 knockdown leads to the accumulation of S1 RNA-binding domain-containing protein 1 (SRBD1), which triggers cellular senescence via AKT1/p53 and RB/p16 pathways, and promotes SASP via NF-κβ pathway in NPCs. Our findings reveal the function and mechanism of selective autophagy receptor NBR1 in regulating NPCs senescence and degeneration. Targeting NBR1 to facilitate the clearance of detrimental substances holds the potential to provide novel insights for IDD treatment.

Keywords: intervertebral disc degeneration, selective autophagy, NBR1, cellular senescence, SRBD1

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