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抑制CD44可通过JAK2/STAT3信号通路抑制脊髓损伤后纤维化瘢痕的形成。

Inhibition of CD44 suppresses the formation of fibrotic scar after spinal cord injury via the JAK2/STAT3 signaling pathway.

作者信息

Guo Jin, Yang Tuo, Zhang Weizhong, Yu Kaiming, Xu Xiong, Li Weizhen, Song Lili, Gu Xiaosong, Cao Rangjuan, Cui Shusen

机构信息

Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China.

Key Laboratory of Peripheral Nerve Injury and Regeneration of Jilin Province, Changchun, Jilin Province 130033, China.

出版信息

iScience. 2024 Jan 16;27(2):108935. doi: 10.1016/j.isci.2024.108935. eCollection 2024 Feb 16.

DOI:10.1016/j.isci.2024.108935
PMID:38323002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10846335/
Abstract

Fibrotic scar is one of the main impediments to axon regeneration following spinal cord injury (SCI). In this study, we found that CD44 was upregulated during the formation of fibrotic scar, and blocking CD44 by IM7 caused downregulation of fibrosis-related extracellular matrix proteins at both 2 and 12 weeks post-spinal cord injury. More Biotinylated dextran amine (BDA)-traced corticospinal tract axons crossed the scar area and extended into the distal region after IM7 administration. A recovery of motor and sensory function was observed based on Basso Mouse Scale (BMS) scores and tail-flick test. experiments revealed that inhibiting CD44 and JAK2/STAT3 signaling pathway decreased the proliferation, differentiation, and migration of fibroblasts induced by the inflammatory supernatant. Collectively, these findings highlight the critical role of CD44 and its downstream JAK2/STAT3 signaling pathway in fibrotic scar formation, suggesting a potential therapeutic target for SCI.

摘要

纤维化瘢痕是脊髓损伤（SCI）后轴突再生的主要障碍之一。在本研究中，我们发现CD44在纤维化瘢痕形成过程中上调，脊髓损伤后2周和12周时，通过IM7阻断CD44可导致纤维化相关细胞外基质蛋白下调。给予IM7后，更多生物素化葡聚糖胺（BDA）标记的皮质脊髓束轴突穿过瘢痕区域并延伸至远端区域。基于Basso小鼠评分量表（BMS）评分和甩尾试验观察到运动和感觉功能有所恢复。实验表明，抑制CD44和JAK2/STAT3信号通路可减少炎性上清液诱导的成纤维细胞增殖、分化和迁移。这些研究结果共同突出了CD44及其下游JAK2/STAT3信号通路在纤维化瘢痕形成中的关键作用，提示其可能成为脊髓损伤的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/456d4ebe7f1e/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/0d0f1d223306/fx1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/46445ba6b352/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/a2e119f163e2/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/32a8ee66578f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/eeb491a48cc3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/2c8b0cbda235/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/2e73dbd5e860/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/456d4ebe7f1e/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/0d0f1d223306/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/6f2e32b0e3b1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/46445ba6b352/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/a2e119f163e2/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/32a8ee66578f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/eeb491a48cc3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/2c8b0cbda235/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/2e73dbd5e860/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7c1/10846335/456d4ebe7f1e/gr8.jpg

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Emerging roles for CNS fibroblasts in health, injury and disease.中枢神经系统成纤维细胞在健康、损伤和疾病中的新作用。
Nat Rev Neurosci. 2022 Jan;23(1):23-34. doi: 10.1038/s41583-021-00525-w. Epub 2021 Oct 20.
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Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions.
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