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胚胎和成体干细胞中环鸟苷酸和一氧化氮途径的调节与药理学

Regulation and Pharmacology of the Cyclic GMP and Nitric Oxide Pathway in Embryonic and Adult Stem Cells.

作者信息

Kots Alexander Y, Bian Ka

机构信息

Veteran Affairs Palo Alto Health Care System, US Department of Veteran Affairs, Palo Alto, CA 90304, USA.

出版信息

Cells. 2024 Dec 5;13(23):2008. doi: 10.3390/cells13232008.

DOI:10.3390/cells13232008
PMID:39682756
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11639989/
Abstract

This review summarizes recent advances in understanding the role of the nitric oxide (NO) and cyclic GMP (cGMP) pathway in stem cells. The levels of expression of various components of the pathway are changed during the differentiation of pluripotent embryonic stem cells. In undifferentiated stem cells, NO regulates self-renewal and survival predominantly through cGMP-independent mechanisms. Natriuretic peptides influence the growth of undifferentiated stem cells by activating particulate isoforms of guanylyl cyclases in a cGMP-mediated manner. The differentiation, recruitment, survival, migration, and homing of partially differentiated precursor cells of various types are sensitive to regulation by endogenous levels of NO and natriuretic peptides produced by stem cells, within surrounding tissues, and by the application of various pharmacological agents known to influence the cGMP pathway. Numerous drugs and formulations target various components of the cGMP pathway to influence the therapeutic efficacy of stem cell-based therapies. Thus, pharmacological manipulation of the cGMP pathway in stem cells can be potentially used to develop novel strategies in regenerative medicine.

摘要

本综述总结了在理解一氧化氮（NO）和环磷酸鸟苷（cGMP）通路在干细胞中的作用方面的最新进展。在多能胚胎干细胞分化过程中，该通路各组分的表达水平会发生变化。在未分化的干细胞中，NO主要通过不依赖cGMP的机制调节自我更新和存活。利钠肽通过以cGMP介导的方式激活鸟苷酸环化酶的颗粒型同工型来影响未分化干细胞的生长。多种类型的部分分化前体细胞的分化、募集、存活、迁移和归巢对干细胞、周围组织产生的内源性NO和利钠肽水平以及应用已知影响cGMP通路的各种药物的调节敏感。众多药物和制剂靶向cGMP通路的各个组分以影响基于干细胞疗法的治疗效果。因此，对干细胞中cGMP通路进行药理学调控有可能用于开发再生医学的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d81/11639989/f3e96368ee7b/cells-13-02008-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d81/11639989/4a26a77c2eec/cells-13-02008-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d81/11639989/f3e96368ee7b/cells-13-02008-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d81/11639989/4a26a77c2eec/cells-13-02008-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d81/11639989/ede3d347b797/cells-13-02008-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d81/11639989/8cffd1242d59/cells-13-02008-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d81/11639989/68ccfbdb0234/cells-13-02008-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d81/11639989/f3e96368ee7b/cells-13-02008-g005.jpg

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Cell Death Differ. 2025 Jan;32(1):149-161. doi: 10.1038/s41418-024-01359-6. Epub 2024 Aug 14.
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iNOS regulates hematopoietic stem and progenitor cells via mitochondrial signaling and is critical for bone marrow regeneration.诱导型一氧化氮合酶通过线粒体信号调节造血干细胞和祖细胞，对骨髓再生至关重要。
Free Radic Biol Med. 2024 Jul;219:184-194. doi: 10.1016/j.freeradbiomed.2024.04.225. Epub 2024 Apr 16.
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Intracellular delivery of nitric oxide enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction.
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Sci Adv. 2023 Dec;9(48):eadi9967. doi: 10.1126/sciadv.adi9967. Epub 2023 Nov 29.
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Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy.基因工程间充质干细胞作为一氧化氮储库治疗急性肾损伤。
Elife. 2023 Sep 11;12:e84820. doi: 10.7554/eLife.84820.
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