CCL2 Knockdown Attenuates Inflammatory Response After Spinal Cord Injury Through the PI3K/Akt Signaling Pathway: Bioinformatics Analysis and Experimental Validation.
Autor: | Fang S; School of Medicine, Lishui University, Lishui, 323000, China., Tang H; Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, #218 Jixi Road, Hefei, 230022, China., Li HL; Department of Orthopedics, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, Anhui, China., Han TC; Department of Orthopedics, The Linquan County People's Hospital, 109 Tong Yang Road, Fuyang, Anhui Province, 236400, People's Republic of China., Li ZJ; Department of Anesthesiology, The Linquan County People's Hospital, 109 Tong Yang Road, Fuyang, Anhui Province, 236400, People's Republic of China., Yin ZS; Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, #218 Jixi Road, Hefei, 230022, China. anhuiyzs@outlook.com., Chu JJ; Department of Orthopedics, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, Anhui, China. chujianjun@163.com. |
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Jazyk: | angličtina |
Zdroj: | Molecular neurobiology [Mol Neurobiol] 2024 Mar; Vol. 61 (3), pp. 1433-1447. Date of Electronic Publication: 2023 Sep 18. |
DOI: | 10.1007/s12035-023-03641-z |
Abstrakt: | Spinal cord injury (SCI) is a common clinical problem in orthopedics with a lack of effective treatments and drug targets. In the present study, we performed bioinformatic analysis of SCI datasets GSE464 and GSE45006 in the Gene Expression Omnibus (GEO) public database and experimentally validated CCL2 expression in an animal model of SCI. This was followed by stimulation of PC-12 cells using hydrogen peroxide to construct a cellular model of SCI. CCL2 expression was knocked down using small interfering RNA (si-CCL2), and PI3K signaling pathway inhibitors and activators were used to validate and observe the changes in downstream inflammation. Through data mining, we found that the inflammatory chemokine CCL2 and PI3K/Akt signaling pathways after SCI expression were significantly increased, and after peroxide stimulation of PC-12 cells with CCL2 knockdown, their downstream cellular inflammatory factor levels were decreased. The PI3K/Akt signaling pathway was blocked by PI3K inhibitors, and the downstream inflammatory response was suppressed. In contrast, when PI3K activators were used, the inflammatory response was enhanced, indicating that the CCL2-PI3K/Akt signaling pathway plays a key role in the regulation of the inflammatory response. This study revealed that the inflammatory chemokine CCL2 can regulate the inflammatory response of PC-12 cells through the PI3K/Akt signaling pathway, and blocking the expression of the inflammatory chemokine CCL2 may be a promising strategy for the treatment of secondary injury after SCI. (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
Databáze: | MEDLINE |
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