Abnormal functional changes in pulmonary artery smooth muscle cells are the main causes of many lung diseases. Among, autophagy plays a crucial role. However, the specific molecular regulatory mechanism of autophagy in PASMCs remains unclear. Here, we first demonstrate that BCAT1 played a key role in the autophagy of hypoxic PASMCs and hypoxic model rats. BCAT1-induced activation and accumulation of the autophagy signaling proteins BECN1 and Atg5 by the endoplasmic reticulum (ER) stress pathway. Interestingly, we discovered that BCAT1 bound IRE1 on the ER to activate expression of its downstream pathway XBP-1-RIDD axis to activate autophagy. More importantly, we identified an RNA-binding protein, zinc finger protein 423, which promoted autophagy by binding adenylate/uridylate (AU)-rich elements in the BCAT1 mRNA 3′-untranslated region. Overall, our results identify BCAT1 as a potential therapeutic target for the clinical treatment of lung diseases and reveal a novel posttranscriptional regulatory mechanism and signaling pathway in hypoxia-induced PASMC autophagy.

肺动脉平滑肌细胞的异常功能变化是许多肺部疾病的主要原因。其中，自噬起着至关重要的作用。然而，PASMCs自噬的具体分子调控机制尚不清楚。在这里，我们首先证明 BCAT1 在缺氧 PASMC 和缺氧模型大鼠的自噬中起关键作用。BCAT1 通过内质网 (ER) 应激途径诱导自噬信号蛋白 BECN1 和 Atg5 的激活和积累。有趣的是，我们发现 BCAT1 结合 ER 上的 IRE1 以激活其下游途径 XBP-1-RIDD 轴的表达以激活自噬。更重要的是，我们鉴定了一种 RNA 结合蛋白，锌指蛋白 423，它通过结合 BCAT1 mRNA 3'-非翻译区中富含腺苷酸/尿苷酸 (AU) 的元件来促进自噬。全面的，