m6A-centered Disease Response Information

General Information of the Disease (ID: M6ADIS0032)
Name
Pulmonary hypertension
ICD
ICD-11: BB01
Full List of Target Gene(s) of This m6A-centered Disease Response
Melanoma-associated antigen D1 (MAGED1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [4]
Response Summary YTHDF1 promotes PASMC proliferation and pulmonary hypertension by enhancing Melanoma-associated antigen D1 (MAGED1) translation.
Responsed Disease Pulmonary hypertension [ICD-11: BB01]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model PASMC cell line (Pulmonary artery smooth muscle cell)
In-vivo Model SMC-specific TWIST1-deficient mice were generated by crossing TWIST1flox/flox mice with animals expressing Sm22-Cre (smooth muscle protein 22-Cre). Deletion of TWIST1 in SMCs was confirmed by histology and Western blot.
Mutated in multiple advanced cancers 1 (PTEN)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [5]
Response Summary METTL3/YTHDF2/Mutated in multiple advanced cancers 1 (PTEN) axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for hypoxic pulmonary hypertension.
Responsed Disease Pulmonary hypertension due to lung disease or hypoxia [ICD-11: BB01.2]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell apoptosis
In-vitro Model PASMC cell line (Pulmonary artery smooth muscle cell)
In-vivo Model 10 rats were divided into control and HPH group. In detail, 5 rats of the hypoxia groups were exposed to hypoxia (10%O2) chamber (AiPu XBS-02B, China) for 4 weeks. In addition, 5 rats of control group were kept under normoxic conditions (21% O2) for 4 weeks. Rats were housed in standard polypropylene cages under controlled photocycle (12 h light/12 h dark) under 22-25 ℃ temperature.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [5]
Response Summary METTL3/YTHDF2/Mutated in multiple advanced cancers 1 (PTEN) axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for hypoxic pulmonary hypertension.
Responsed Disease Pulmonary hypertension due to lung disease or hypoxia [ICD-11: BB01.2]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell apoptosis
In-vitro Model PASMC cell line (Pulmonary artery smooth muscle cell)
In-vivo Model 10 rats were divided into control and HPH group. In detail, 5 rats of the hypoxia groups were exposed to hypoxia (10%O2) chamber (AiPu XBS-02B, China) for 4 weeks. In addition, 5 rats of control group were kept under normoxic conditions (21% O2) for 4 weeks. Rats were housed in standard polypropylene cages under controlled photocycle (12 h light/12 h dark) under 22-25 ℃ temperature.
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Disease
In total 1 item(s) under this disease
Crosstalk ID: M6ACROT02013
 Crosstalk Info 
m6A Regulator YTH domain-containing protein 1 (YTHDC1)
 Regulator Info 
m6A Target FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR)
 Target Gene 
Regulated Target Dynamin-1-like protein (DRP1)
Crosstalk relationship m6A → DNA modification
References
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Ref 2 The role of human CYP2C8 and CYP2C9 variants in pioglitazone metabolism in vitro. Basic Clin Pharmacol Toxicol. 2009 Dec;105(6):374-9. doi: 10.1111/j.1742-7843.2009.00457.x. Epub 2009 Jul 15.
Ref 3 Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J Med Chem. 2006 Oct 19;49(21):6139-42. doi: 10.1021/jm060460o.
Ref 4 YTHDF1 Regulates Pulmonary Hypertension through Translational Control of MAGED1. Am J Respir Crit Care Med. 2021 May 1;203(9):1158-1172. doi: 10.1164/rccm.202009-3419OC.
Ref 5 The m(6)A methyltransferase METTL3 promotes hypoxic pulmonary arterial hypertension. Life Sci. 2021 Jun 1;274:119366. doi: 10.1016/j.lfs.2021.119366. Epub 2021 Mar 16.
Ref 6 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025396)
Ref 7 QSAR analysis and molecular modeling of ABCG2-specific inhibitors. Adv Drug Deliv Rev. 2009 Jan 31;61(1):34-46.
Ref 8 Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone. Br J Clin Pharmacol. 1999 Sep;48(3):424-32. doi: 10.1046/j.1365-2125.1999.00030.x.