Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair
The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain. In many cases, the microenvironment surrounding demyelination lesions contains inhibitory molecules, which lead to repair failure. Accordingly, blocking the activity of th...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=4;spage=832;epage=839;aulast=Xiong |
| _version_ | 1828133271979950080 |
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| author | Ya-Jie Xiong Shahid Hussain Soomro Zhong-Hai Huang Pan-Pan Yu Jie Ping Hui Fu |
| author_facet | Ya-Jie Xiong Shahid Hussain Soomro Zhong-Hai Huang Pan-Pan Yu Jie Ping Hui Fu |
| author_sort | Ya-Jie Xiong |
| collection | DOAJ |
| description | The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain. In many cases, the microenvironment surrounding demyelination lesions contains inhibitory molecules, which lead to repair failure. Accordingly, blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination. In the central nervous system, oligodendrocytes form the myelin sheath. We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation. Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function. Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation, as well as PI3K signaling pathways that are needed in the mid-late stages. When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination, it enhanced myelin regeneration and promoted motor function recovery. These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury. |
| first_indexed | 2024-04-11T17:17:13Z |
| format | Article |
| id | doaj.art-b785b3ce43934ee5b8ab5ad9ba6ce8ae |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-11T17:17:13Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-b785b3ce43934ee5b8ab5ad9ba6ce8ae2022-12-22T04:12:36ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742023-01-0118483283910.4103/1673-5374.353493Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repairYa-Jie XiongShahid Hussain SoomroZhong-Hai HuangPan-Pan YuJie PingHui FuThe extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain. In many cases, the microenvironment surrounding demyelination lesions contains inhibitory molecules, which lead to repair failure. Accordingly, blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination. In the central nervous system, oligodendrocytes form the myelin sheath. We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation. Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function. Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation, as well as PI3K signaling pathways that are needed in the mid-late stages. When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination, it enhanced myelin regeneration and promoted motor function recovery. These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=4;spage=832;epage=839;aulast=Xiongdifferentiation; erk1/2; extracellular matrix; fibronectin; lysolecithin-induced demyelination; oligodendrocyte; pi3k; poly-l-ornithine; proliferation; remyelination |
| spellingShingle | Ya-Jie Xiong Shahid Hussain Soomro Zhong-Hai Huang Pan-Pan Yu Jie Ping Hui Fu Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair Neural Regeneration Research differentiation; erk1/2; extracellular matrix; fibronectin; lysolecithin-induced demyelination; oligodendrocyte; pi3k; poly-l-ornithine; proliferation; remyelination |
| title | Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair |
| title_full | Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair |
| title_fullStr | Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair |
| title_full_unstemmed | Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair |
| title_short | Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair |
| title_sort | poly l ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair |
| topic | differentiation; erk1/2; extracellular matrix; fibronectin; lysolecithin-induced demyelination; oligodendrocyte; pi3k; poly-l-ornithine; proliferation; remyelination |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=4;spage=832;epage=839;aulast=Xiong |
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