Despite the debilitating and lethal nature of pulmonary hypertension (PH) secondary to interstitial lung disease (group 3 PH),1 research into the treatment of this unique category of vasculopathy remains in a relatively nascent stage compared with that of pulmonary arterial hypertension (PAH, group 1). A clue to uncovering the underlying pathophysiology of this particular subtype of group 3 PH, however, may be found in overlapping interest in the DNA damage response (DDR) shared by both pulmonary fibrosis and PH researchers.2 Primarily a pathway dedicated to preventing DNA damage to cellular progeny, the DDR functions via a complex network of cell cycle checkpoint signalling and DNA repair mechanisms. In the context of malignancy, these non-redundant pathways can be exploited by dependent cancerous cells to thwart apoptosis, thus promoting survival and eventual metastasis. Therapeutically, a key target of the DDR is the family of checkpoint kinases: CHK1 primarily affecting the prevention of DNA damage being replicated (resulting in G1/S-phase cell cycle arrest), and CHK2 mediating transmission to the next generation of cells (a G2/M-phase checkpoint).3 While there are examples of CHK regulation related to end-organ fibrosis, to date, there is a dearth of literature describing the role of CHK in lung fibrosis. …

中文翻译：

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CHK 自己，在你毁掉自己之前：针对继发性肺动脉高压的 DNA 损伤反应

尽管继发于间质性肺病（第 3 组 PH）的肺动脉高压 (PH) 具有使人虚弱和致命的性质，1 但与肺动脉高压（PAH、第 1 组）。然而，揭示第 3 组 PH 的这种特定亚型的潜在病理生理学的线索可能是肺纤维化和 PH 研究人员对 DNA 损伤反应 (DDR) 的共同兴趣。 2 主要是一种致力于预防 DNA 损伤的途径对于细胞后代，DDR 通过细胞周期检查点信号和 DNA 修复机制的复杂网络发挥作用。在恶性肿瘤的背景下，依赖性癌细胞可以利用这些非冗余途径来阻止细胞凋亡，从而促进生存和最终转移。在治疗上，DDR 的一个关键目标是检查点激酶家族：CHK1 主要影响防止 DNA 损伤被复制（导致 G1/S 期细胞周期停滞），而 CHK2 介导传递到下一代细胞（a G2/M 期检查点）。3 虽然有 CHK 调节与终末器官纤维化相关的例子，但迄今为止，描述 CHK 在肺纤维化中的作用的文献很少。…… 3 虽然有 CHK 调节与终末器官纤维化相关的例子，但迄今为止，描述 CHK 在肺纤维化中的作用的文献还很缺乏。…… 3 虽然有 CHK 调节与终末器官纤维化相关的例子，但迄今为止，描述 CHK 在肺纤维化中的作用的文献还很缺乏。……