Profiling the miRNA from Exosomes of Non-Pigmented Ciliary Epithelium-Derived Identifies Key Gene Targets Relevant to Primary Open-Angle Glaucoma.
Profiling the miRNA from Exosomes of Non-Pigmented Ciliary Epithelium-Derived Identifies Key Gene Targets Relevant to Primary Open-Angle Glaucoma.
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DOI：
10.3390/antiox12020405
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发表时间：
2023-02-07
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影响因子：
--
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中科院分区：
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组织氧化应激(OS)是导致眼压升高和原发性开角型青光眼(POAG)的主要病理损伤。由非色素睫状体上皮(NPCE)产生的房水通过前房小梁网(TM)流出途径流出。外切体是AH的主要成分，外切体可以调节信号事件，也可以调节其靶TM组织的反应。尽管存在否定OS的分子机制，但氧化损伤直接和间接地影响TM的健康、AH引流和IOP。我们认为，OS可以影响AH中外切小体携带的microRNA(MiRNAs)的表达，从而调节靶细胞的信号转导途径。为了评估这一点，我们对NPCE进行了急性和慢性OS(A-OS和C-OS)，丰富了miRNAs，进行了miRNA芯片分析，并进行了基于miRNA的基因靶向通路预测分析。我们发现包括miR27、miR199、miR23、miR130b和miR200在内的各种miRNA家族都发生了显著的变化。基于路径预测分析，我们发现这些miRNAs可以调控包括Nrf2、Keap1、GSK3B和丝氨酸/苏氨酸蛋白磷酸酶2A(PP2A)在内的基因。我们认为，NPCE外体miRNA载体上的OS可以调节TM组织的功能。
Oxidative stress (OS) on tissues is a major pathological insult leading to elevated intraocular pressure (IOP) and primary open-angle glaucoma (POAG). Aqueous humor (AH) produced by the non-pigmentary ciliary epithelium (NPCE) drains out via the trabecular meshwork (TM) outflow pathway in the anterior chamber. The exosomes are major constituents of AH, and exosomes can modulate the signaling events, as well as the responses of their target TM tissue. Despite the presence of molecular mechanisms to negate OS, oxidative damage directly, as well as indirectly, influences TM health, AH drainage, and IOP. We proposed that the expression of microRNA (miRNAs) carried by exosomes in the AH can be affected by OS, and this can modulate the pathways in target cells. To assess this, we subjected NPCE to acute and chronic OS (A-OS and C-OS), enriched miRNAs, performed miRNA microarray chip analyses, and miRNA-based gene targeting pathway prediction analysis. We found that various miRNA families, including miR27, miR199, miR23, miR130b, and miR200, changed significantly. Based on pathway prediction analysis, we found that these miRNAs can regulate the genes including Nrf2, Keap1, GSK3B, and serine/threonine-protein phosphatase2A (PP2A). We propose that OS on the NPCE exosomal miRNA cargo can modulate the functionality of the TM tissue.
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DOI：
10.1073/pnas.83.22.8754
发表时间：
1986-11-01
影响因子：
11.1
作者：
COCAPRADOS, M;WAX, MB
通讯作者：
WAX, MB
影响因子：
14.9
作者：
Karagkouni D;Paraskevopoulou MD;Chatzopoulos S;Vlachos IS;Tastsoglou S;Kanellos I;Papadimitriou D;Kavakiotis I;Maniou S;Skoufos G;Vergoulis T;Dalamagas T;Hatzigeorgiou AG
通讯作者：
Hatzigeorgiou AG
影响因子：
5.6
作者：
Lerner N;Chen I;Schreiber-Avissar S;Beit-Yannai E
通讯作者：
Beit-Yannai E
影响因子：
3.7
作者：
Hedlund M;Nagaeva O;Kargl D;Baranov V;Mincheva-Nilsson L
通讯作者：
Mincheva-Nilsson L
影响因子：
3
作者：
Ben Or G;Veksler-Lublinsky I
通讯作者：
Veksler-Lublinsky I