American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2021
YTHDF1 Regulates Pulmonary Hypertension Through Translational Control of MAGED1.
Rationale: Posttranscriptional modifications are implicated in vascular remodeling of pulmonary hypertension (PH). m6A (N6-methyladenosine) is an abundant RNA modification that is involved in various biological processes. Whether m6A RNA modification and m6A effector proteins play a role in pulmonary vascular remodeling and PH has not been demonstrated. Objectives: To determine whether m6A modification and m6A effectors contribute to the pathogenesis of PH. ⋯ In addition, MAGED1 silencing inhibited hypoxia-induced proliferation of PASMCs through downregulating PCNA. Conclusions: YTHDF1 promotes PASMC proliferation and PH by enhancing MAGED1 translation. This study identifies the m6A RNA modification as a novel mediator of pathological changes in PASMCs and PH.