Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation
Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the phys...
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MDPI AG
2023-04-01
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| author | Chiung-Hui Liu Ying-Jui Ho Che-Yu Wang Chao-Chun Hsu Yin-Hung Chu Min-Yen Hsu Shiu-Jau Chen Wen-Chuan Hsiao Wen-Chieh Liao |
| author_facet | Chiung-Hui Liu Ying-Jui Ho Che-Yu Wang Chao-Chun Hsu Yin-Hung Chu Min-Yen Hsu Shiu-Jau Chen Wen-Chuan Hsiao Wen-Chieh Liao |
| author_sort | Chiung-Hui Liu |
| collection | DOAJ |
| description | Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration. |
| first_indexed | 2024-03-11T04:11:52Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T04:11:52Z |
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| spelling | doaj.art-1e2245886c1b4fa49fcf6a1c9cfb4f222023-11-17T23:22:51ZengMDPI AGMolecules1420-30492023-04-01289374210.3390/molecules28093742Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican AccumulationChiung-Hui Liu0Ying-Jui Ho1Che-Yu Wang2Chao-Chun Hsu3Yin-Hung Chu4Min-Yen Hsu5Shiu-Jau Chen6Wen-Chuan Hsiao7Wen-Chieh Liao8Ph.D. Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, TaiwanDepartment of Psychology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd., Taichung 402306, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 402306, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 402306, TaiwanPh.D. Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 402306, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City 252005, TaiwanDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, TaiwanPh.D. Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, TaiwanVersican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration.https://www.mdpi.com/1420-3049/28/9/3742Chsy1versicannerve regenerationend-to-side neurorrhaphyperipheral nerve injurySchwann cells |
| spellingShingle | Chiung-Hui Liu Ying-Jui Ho Che-Yu Wang Chao-Chun Hsu Yin-Hung Chu Min-Yen Hsu Shiu-Jau Chen Wen-Chuan Hsiao Wen-Chieh Liao Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation Molecules Chsy1 versican nerve regeneration end-to-side neurorrhaphy peripheral nerve injury Schwann cells |
| title | Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation |
| title_full | Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation |
| title_fullStr | Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation |
| title_full_unstemmed | Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation |
| title_short | Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation |
| title_sort | targeting chondroitin sulphate synthase 1 chsy1 promotes axon growth following neurorrhaphy by suppressing versican accumulation |
| topic | Chsy1 versican nerve regeneration end-to-side neurorrhaphy peripheral nerve injury Schwann cells |
| url | https://www.mdpi.com/1420-3049/28/9/3742 |
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