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三叉神经衍生的P物质通过PI3K-AKT途径调节角膜缘干细胞。

Trigeminal nerve-derived substance P regulates limbal stem cells by the PI3K-AKT pathway.

作者信息

Xu Peipei, Lin Xiongshi, Dong Xing, Liu Ying, Wang Zhichong, Wang Shuangyong

机构信息

The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong Province, China.

出版信息

iScience. 2023 Apr 18;26(5):106688. doi: 10.1016/j.isci.2023.106688. eCollection 2023 May 19.

DOI:10.1016/j.isci.2023.106688
PMID:37187698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10176256/
Abstract

Trigeminal nerve-derived substance P (SP), a widespread neuropeptide, is known to maintain the corneal epithelial homeostasis and promote the closure of wound healing. Using comprehensive and assays and RNA-sequencing analysis, we aimed to unveil the positive effects of SP on the biological characteristics of limbal stem cells (LSCs) and the underlying mechanism. SP enhanced the proliferation and stemness of LSCs Correspondingly, it rescued corneal defects, corneal sensitivity, and the expression of LSC-positive markers in a neurotrophic keratopathy (NK) mouse model . Topical injection of a neurokinin-1 receptor (NK1R) antagonist caused similar pathological changes as in corneal denervated mice and attenuated LSC-positive markers levels. Mechanistically, we revealed that SP regulated LSCs functions by modulating the PI3K-AKT pathway. Our findings showed that the trigeminal nerve regulates LSCs by releasing SP, which may provide new insights into the regulation of LSCs' fate and stem cell therapy.

摘要

三叉神经衍生的P物质（SP）是一种广泛存在的神经肽，已知其可维持角膜上皮的稳态并促进伤口愈合的闭合。我们使用综合分析和RNA测序分析，旨在揭示SP对角膜缘干细胞（LSCs）生物学特性的积极影响及其潜在机制。SP增强了LSCs的增殖和干性。相应地，在神经营养性角膜病变（NK）小鼠模型中，它挽救了角膜缺损、角膜敏感性以及LSC阳性标志物的表达。局部注射神经激肽-1受体（NK1R）拮抗剂会引起与角膜去神经支配小鼠相似的病理变化，并降低LSC阳性标志物水平。从机制上讲，我们发现SP通过调节PI3K-AKT途径来调节LSCs的功能。我们的研究结果表明，三叉神经通过释放SP来调节LSCs，这可能为LSCs命运的调控和干细胞治疗提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/7d1ececa5b32/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/2618668d3422/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/0156aa9888c0/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/cfea9a4fc398/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/23cf9c9e0fa6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/57738bfbbc5a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/3a66826cfd37/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/7d1ececa5b32/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/2618668d3422/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/0156aa9888c0/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/cfea9a4fc398/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/23cf9c9e0fa6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/57738bfbbc5a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/3a66826cfd37/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/10176256/7d1ececa5b32/gr6.jpg

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本文引用的文献

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2
Substance P/neurokinin-1 receptor pathway blockade ameliorates limbal stem cell deficiency by modulating mTOR pathway and preventing cell senescence.物质 P/神经激肽-1 受体通路阻断通过调节 mTOR 通路和防止细胞衰老改善角膜缘干细胞缺乏。
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Human limbal epithelial stem cell regulation, bioengineering and function.
人角膜缘上皮干细胞的调控、生物工程和功能。
Prog Retin Eye Res. 2021 Nov;85:100956. doi: 10.1016/j.preteyeres.2021.100956. Epub 2021 Mar 4.
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Agrin Promotes Limbal Stem Cell Proliferation and Corneal Wound Healing Through Hippo-Yap Signaling Pathway.Agrin 通过 Hippo-Yap 信号通路促进角膜缘干细胞增殖和角膜伤口愈合。
Invest Ophthalmol Vis Sci. 2020 May 11;61(5):7. doi: 10.1167/iovs.61.5.7.
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Akt modes of stem cell regulation: more than meets the eye?Akt调节干细胞的方式：不止表面所见？
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