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马钱子碱诱导肺动脉高压大鼠 mA mRNA 甲基化的综合分析。

Integrated analysis of mA mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension.

机构信息

Academy of Pediatrics, University of South China, Changsha 410007, China.

Department of Cardiology, Hunan Children's Hospital, Changsha 410007, China.

出版信息

Aging (Albany NY). 2021 Jul 26;13(14):18238-18256. doi: 10.18632/aging.203230.

DOI:10.18632/aging.203230
PMID:34310344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8351682/
Abstract

BACKGROUND

N6-methyladenosine (mA) modification is one of the most common chemical modifications of eukaryotic mRNAs, which play an important role in tumors and cardiovascular disease through regulating mRNA stability, splicing and translation. However, the changes of mA mRNA and mA-related enzymes in pulmonary arterial hypertension (PAH) remain largely unexplored.

METHODS

MeRIP-seq was used to identify mA methylation in lung tissues from control and MCT-PAH rats. Western blot and immunofluorescence were used to evaluate expression of mA-related enzymes.

RESULTS

Compared with control group, mA methylation was mainly increased in lung tissues from MCT-PAH rats. The up-methylated coding genes in MCT-PAH rats were primarily enriched in processes associated with inflammation, glycolysis, ECM-receptor interaction and PDGF signal pathway, while genes with down-methylation were enriched in processes associated with TGF-β family receptor members. The expression of FTO and ALKBH5 downregulated, METTL3 and YTHDF1 increased and other methylation modification-related proteins was not significantly changed in MCT-PAH rats lung tissues. Immunofluorescence indicated that expression of FTO decreased and YTHDF1 increased in small pulmonary arteries of MCT-PAH rats.

CONCLUSION

mA levels and the expression of methylation-related enzymes were altered in PAH rats, in which FTO and YTHDF1 may play a crucial role in mA modification.

摘要

背景

N6-甲基腺苷（mA）修饰是真核 mRNA 中最常见的化学修饰之一，通过调节 mRNA 稳定性、剪接和翻译，在肿瘤和心血管疾病中发挥重要作用。然而，肺动脉高压（PAH）中 mA mRNA 和 mA 相关酶的变化在很大程度上仍未得到探索。

方法

使用 MeRIP-seq 鉴定对照和 MCT-PAH 大鼠肺组织中的 mA 甲基化。Western blot 和免疫荧光法用于评估 mA 相关酶的表达。

结果

与对照组相比，MCT-PAH 大鼠肺组织中的 mA 甲基化主要增加。MCT-PAH 大鼠中上调甲基化的编码基因主要富集在与炎症、糖酵解、ECM-受体相互作用和 PDGF 信号通路相关的过程中，而下调甲基化的基因则富集在与 TGF-β 家族受体成员相关的过程中。FTO 和 ALKBH5 的表达下调，METTL3 和 YTHDF1 增加，而 MCT-PAH 大鼠肺组织中其他甲基化修饰相关蛋白没有明显变化。免疫荧光表明，FTO 在 MCT-PAH 大鼠的小肺动脉中表达减少，YTHDF1 增加。

结论

mA 水平和甲基化相关酶的表达在 PAH 大鼠中发生改变，其中 FTO 和 YTHDF1 可能在 mA 修饰中发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/04424ed6ab09/aging-13-203230-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/87ab5a14650e/aging-13-203230-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/aba58d063f01/aging-13-203230-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/26b8a86df714/aging-13-203230-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/461f1513a0b5/aging-13-203230-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/5fbd7c8ade41/aging-13-203230-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/04424ed6ab09/aging-13-203230-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/87ab5a14650e/aging-13-203230-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/aba58d063f01/aging-13-203230-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/26b8a86df714/aging-13-203230-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/461f1513a0b5/aging-13-203230-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/5fbd7c8ade41/aging-13-203230-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d425/8351682/04424ed6ab09/aging-13-203230-g006.jpg

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