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B1重复序列甲基化增强大鼠二度烧伤的伤口愈合。

B1 repetitive sequence methylation enhances wound healing of second-degree burns in rats.

作者信息

Meevassana Jiraroch, Nacharoenkul Panupong, Wititsuwannakul Jade, Kitkumthorn Nakarin, Hamill Kevin J, Angspatt Apichai, Mutirangura Apiwat

机构信息

Department of Anatomy, Center of Excellence in Molecular Genetics of Cancer and Human Disease, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Department of Surgery, Division of Plastic and Reconstructive Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

出版信息

Biomed Rep. 2022 Mar;16(3):20. doi: 10.3892/br.2022.1503. Epub 2022 Feb 3.

DOI:10.3892/br.2022.1503
PMID:35251607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8850962/
Abstract

The accumulation of DNA damage in burn wounds delays wound healing. DNA methylation by short interspersed nuclear element (SINE) small interfering (si)RNA prevents DNA damage and promotes cell proliferation. Therefore, SINE siRNA may be able to promote burn wound healing. Here, a SINE B1 siRNA was used to treat burn wounds in rats. Second-degree burn wounds were introduced on the backs of rats. The rats were then divided into three groups: a B1 siRNA-treated, saline-treated control, and saline + calcium phosphate-nanoparticle-treated control group (n=15/group). The wounds were imaged on days 0, 7, 14, 21 and 28 post-injury. The tissue sections were processed for methylation, histological and immunohistochemical examination, and scored based on the overall expression of histone H2AX phosphorylated on serine 139 (γH2AX) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Burn wound closure improved in the B1 siRNA-treated group compared with that in the control group, especially from days 14-28 post-injury (P<0.001). The overall pathological score and degree of B1 methylation in the B1 siRNA-treated group improved significantly at days 14-28 post-injury, with the maximum improvement observed on day 14 (P<0.01) compared with the NSS and Ca-P nanoparticle groups. Immunohistochemical staining revealed lower expression of γH2AX and 8-OHdG in the B1 siRNA-treated group than in the control groups at days 14-28 post-injury; the maximum improvement was observed on days 14 and 21. These data imply that administering SINE siRNA is a promising therapeutic option for managing second-degree burns.

摘要

烧伤创面中DNA损伤的积累会延迟伤口愈合。短散在核元件(SINE)小干扰(si)RNA介导的DNA甲基化可防止DNA损伤并促进细胞增殖。因此,SINE siRNA或许能够促进烧伤创面愈合。在此,使用一种SINE B1 siRNA来治疗大鼠烧伤创面。在大鼠背部造成二度烧伤创面。然后将大鼠分为三组:B1 siRNA治疗组、生理盐水治疗对照组和生理盐水+磷酸钙纳米颗粒治疗对照组(每组n = 15)。在伤后第0、7、14、21和28天对创面进行成像。对组织切片进行甲基化、组织学和免疫组织化学检查,并根据丝氨酸139磷酸化的组蛋白H2AX(γH2AX)和8-羟基-2'-脱氧鸟苷(8-OHdG)的整体表达进行评分。与对照组相比,B1 siRNA治疗组的烧伤创面愈合情况有所改善,尤其是在伤后14 - 28天(P < 0.001)。在伤后14 - 28天,B1 siRNA治疗组的总体病理评分和B1甲基化程度显著改善,与生理盐水和磷酸钙纳米颗粒组相比,在第14天观察到最大改善(P < 0.01)。免疫组织化学染色显示,在伤后14 - 28天,B1 siRNA治疗组中γH2AX和8-OHdG的表达低于对照组;在第14天和21天观察到最大改善。这些数据表明,给予SINE siRNA是治疗二度烧伤的一种有前景的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/8850962/a61d8ba5859c/br-16-03-01503-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/8850962/fca40b8bf149/br-16-03-01503-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/8850962/17611267e759/br-16-03-01503-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/8850962/a61d8ba5859c/br-16-03-01503-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/8850962/fca40b8bf149/br-16-03-01503-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/8850962/17611267e759/br-16-03-01503-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/8850962/a61d8ba5859c/br-16-03-01503-g02.jpg

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RNA-directed DNA Methylation.RNA 指导的 DNA 甲基化。
PLoS Genet. 2020 Oct 8;16(10):e1009034. doi: 10.1371/journal.pgen.1009034. eCollection 2020 Oct.
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Calcium Phosphate Nanoparticles-Based Systems for RNAi Delivery: Applications in Bone Tissue Regeneration.
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Environ Pollut. 2020 Apr;259:113840. doi: 10.1016/j.envpol.2019.113840. Epub 2019 Dec 19.
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Chromatin Remodeling and Epigenetic Regulation in Plant DNA Damage Repair.染色质重塑和表观遗传调控在植物 DNA 损伤修复中的作用。
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Argonaute 4 as an Effector Protein in RNA-Directed DNA Methylation in Human Cells.人类细胞中作为RNA指导的DNA甲基化效应蛋白的AGO4(Argonaute 4)
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