GPNMB Modulates Autophagy to Enhance Functional Recovery After Spinal Cord Injury in Rats

• Published in: Cell transplantation 2024-01, Vol.33, p.9636897241233040-9636897241233040
• Main Authors: Li, Xixi, Xu, Jiakun, Su, Weijie, Su, Luoxi, Chen, Xiangkun, Yang, Jia, Lin, Xunxun, Yang, Lixuan
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Autophagy; Cell injury; Enzyme-linked immunosorbent assay; Expression vectors; Glutathione; Glutathione - metabolism; Glycoproteins - pharmacology; Humans; Immunofluorescence; Inflammation; Lipopolysaccharides; Melanoma; Melanoma - metabolism; Melanoma - pathology; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - pharmacology; Metastases; Neuroprotection; Original; Oxidative stress; Protein B; Quality of Life; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Receptors, Fc; Recovery of function; Recovery of Function - physiology; Regeneration; Spinal Cord - pathology; Spinal cord injuries; Spinal Cord Injuries - pathology
• ISSN: 0963-6897; 1555-3892
• DOI: 10.1177/09636897241233040

Spinal cord injury (SCI) severely affects the quality of life and autonomy of patients, and effective treatments are currently lacking. Autophagy, an essential cellular metabolic process, plays a crucial role in neuroprotection and repair after SCI. Glycoprotein non-metastatic melanoma protein B (GPNMB) has been shown to promote neural regeneration and synapse reconstruction, potentially through the facilitation of autophagy. However, the specific role of GPNMB in autophagy after SCI is still unclear. In this study, we utilized the spinal cord transection method to establish SCI rats model and overexpressed GPNMB using adenoviral vectors. We assessed tissue damage using hematoxylin and eosin (H&E) and Nissl staining, and observed cell apoptosis using TUNEL staining. We evaluated the inflammatory response by measuring inflammatory factors using enzyme-linked immunosorbent assay (ELISA). In addition, we measured reactive oxygen species (ROS) levels using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA), and assessed oxidative stress levels by measuring malondialdehyde (MDA) and glutathione (GSH) using ELISA. To evaluate autophagy levels, we performed immunofluorescence staining for the autophagy marker Beclin-1 and conducted Western blot analysis for autophagy-related proteins. We also assessed limb recovery through functional evaluation. Meanwhile, we induced cell injury using lipopolysaccharide (LPS) and added an autophagy inhibitor to verify the impact of GPNMB on SCI through autophagy modulation. The results demonstrated that GPNMB alleviated the inflammatory response, reduced oxidative stress levels, inhibited cell apoptosis, and promoted autophagy following SCI. Inhibiting autophagy reversed the effects of GPNMB. These findings suggest that GPNMB promotes neural injury repair after SCI, potentially through attenuating the inflammatory response, reducing oxidative stress, and inhibiting cell apoptosis.