Dataset Information

Integrated analysis of m⁶A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension.

ABSTRACT:

Background

N6-methyladenosine (m⁶A) 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 m⁶A mRNA and m⁶A-related enzymes in pulmonary arterial hypertension (PAH) remain largely unexplored.

Methods

MeRIP-seq was used to identify m⁶A methylation in lung tissues from control and MCT-PAH rats. Western blot and immunofluorescence were used to evaluate expression of m⁶A-related enzymes.

Results

Compared with control group, m⁶A 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

m⁶A levels and the expression of methylation-related enzymes were altered in PAH rats, in which FTO and YTHDF1 may play a crucial role in m⁶A modification.

SUBMITTER: Zeng Y

PROVIDER: S-EPMC8351682 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Integrated analysis of m<sup>6</sup>A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension.

Zeng Yunhong Y Huang Ting T Zuo Wanyun W Wang Dan D Xie Yonghui Y Wang Xun X Xiao Zhenghui Z Chen Zhi Z Liu Qiming Q Liu Na N Xiao Yunbin Y

Aging 20210726 14

<h4>Background</h4>N6-methyladenosine (m<sup>6</sup>A) 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 m<sup>6</sup>A mRNA and m<sup>6</sup>A-related enzymes in pulmonary arterial hypertension (PAH) remain largely unexplored.<h4>Methods</h4>MeRIP-seq was used to identify m<sup>6</sup>A methylation in lung tissues ...[more]

PMID: 34310344

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Project description:BackgroundDapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), can reduce cardiovascular events and mortality in patients with heart failure. A number of mechanisms have been proposed to explain the beneficial effects of SGLT2 inhibitors. The purpose of this study was to determine whether dapagliflozin can improve pulmonary vascular remodelling and the efficacy of dapagliflozin as an add-on therapy to sildenafil in rats with pulmonary arterial hypertension (PAH).MethodsA monocrotaline (MCT)-induced PAH rat model was used in our study. MCT-injected rats were randomly divided into four groups and treated for 3 weeks with daily per os treatment with vehicle, dapagliflozin (1 mg/kg/day), sildenafil (25 mg/kg/day), or a combination of dapagliflozin (1 mg/kg/day) and sildenafil (25 mg/kg/day). Haemodynamic measurements, histological analysis, enzyme-linked immunosorbent assay and western blotting analysis were employed to detect the changes in PAH rats after treatments.ResultsDapagliflozin significantly attenuated MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) in PAH rats. Dapagliflozin effectively decreased the thickening of pulmonary artery media and decreased the muscularization of pulmonary arterioles in PAH rats. Moreover, dapagliflozin attenuated nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in lung tissues and the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in plasma. However, dapagliflozin as an add-on therapy to sildenafil in rats with PAH did not show a more pronounced beneficial effect on right ventricular systolic pressure and pulmonary vascular remodelling in MCT rats than sildenafil alone.ConclusionsDapagliflozin reduces right ventricular systolic pressure and pulmonary vascular remodelling in a rat model of PAH. However, combination therapy with dapagliflozin and sildenafil was not more effective than monotherapy with sildenafil in PAH rats.

Dataset Information

Integrated analysis of m⁶A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension.

Background

Methods

Results

Conclusion

Publications

Integrated analysis of m<sup>6</sup>A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Integrated analysis of m6A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension.

Background

Methods

Results

Conclusion

Publications

Integrated analysis of m<sup>6</sup>A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Integrated analysis of m⁶A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension.