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)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
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
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)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
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
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 [2]
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
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.
References
Ref 1 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 2 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.