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miR-30b 通过 Sema3A/NRP-1/PlexinA1/RhoA/ROCK 通路促进脊髓感觉功能恢复。

miR-30b Promotes spinal cord sensory function recovery via the Sema3A/NRP-1/PlexinA1/RhoA/ROCK Pathway.

机构信息

Chengde Medical University, Chengde, China.

Department of Orthopedics, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China.

出版信息

J Cell Mol Med. 2020 Nov;24(21):12285-12297. doi: 10.1111/jcmm.15591. Epub 2020 Sep 25.

DOI:10.1111/jcmm.15591
PMID:32977360
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7686968/
Abstract

Spinal cord injury (SCI) induces both motor and sensory dysfunctions. We wondered whether miR-30b could promote primary sensory neuron (PSN) axon growth in inhibitory microenvironment. The neurite growth was promoted by miR-30b agomir and inhibited by antagomir. MiR-30b targeted and degraded sema3A mRNA. MiR-30b regulated the formation of sema3A-NRP-1-PlexinA1 complex via targeting sema3A. The neurite length was induced by the miR-30b agomir, and the application of sema3A protein could reverse the effect of agomir. GTP-RhoA and ROCK expression were down-regulated by miR-30b. Neurite outgrowth that inhibited by sema3A and the miR-30b antagomir was increased by Y-27632. Agomir promoted neurite growth in NogoA inhibitory conditions, which indicated miR-30b could both enhance neuronal intrinsic regenerative ability and promote neurite growth against inhibitory microenvironment via Sema3A/NRP-1/PlexinA1/RhoA/ROCK axis. The agomir could also regulate Sema3A/NRP-1/PlexinA1/RhoA/ROCK axis in vivo and restore spinal cord sensory conductive function. In conclusion, miR-30b could be a novel target for sensation recovery after SCI.

摘要

脊髓损伤 (SCI) 可引起运动和感觉功能障碍。我们想知道 miR-30b 是否能在抑制性微环境中促进初级感觉神经元 (PSN) 轴突生长。miR-30b 激动剂促进神经突生长，而拮抗剂则抑制神经突生长。miR-30b 靶向并降解了 sema3A mRNA。miR-30b 通过靶向 sema3A 调节 sema3A-NRP-1-PlexinA1 复合物的形成。miR-30b 激动剂诱导神经突长度增加，而 sema3A 蛋白的应用可逆转激动剂的作用。miR-30b 下调 GTP-RhoA 和 ROCK 的表达。sema3A 和 miR-30b 拮抗剂抑制的神经突生长通过 Y-27632 增加。激动剂在 NogoA 抑制条件下促进神经突生长，表明 miR-30b 既能增强神经元内在的再生能力，又能通过 Sema3A/NRP-1/PlexinA1/RhoA/ROCK 轴促进神经突生长对抗抑制性微环境。激动剂还可以在体内调节 Sema3A/NRP-1/PlexinA1/RhoA/ROCK 轴，恢复脊髓感觉传导功能。总之，miR-30b 可能是 SCI 后感觉恢复的一个新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dd/7686968/9c90f316119a/JCMM-24-12285-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dd/7686968/73853cf90467/JCMM-24-12285-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dd/7686968/9c90f316119a/JCMM-24-12285-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dd/7686968/97624363b89a/JCMM-24-12285-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dd/7686968/41cab9c04df1/JCMM-24-12285-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dd/7686968/ee159e14e3c9/JCMM-24-12285-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dd/7686968/8fbe82785a58/JCMM-24-12285-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dd/7686968/73853cf90467/JCMM-24-12285-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dd/7686968/9c90f316119a/JCMM-24-12285-g008.jpg

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