School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, and Immune Health program, Hunter Medical Research Institute (HMRI), Newcastle, New South Wales, Australia.
School of Life Sciences, University of Technology Sydney, and the Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
J Clin Invest. 2022 Jun 1;132(11). doi: 10.1172/JCI160595.
Although aging and lung injury are linked to the development of idiopathic pulmonary fibrosis (IPF), the underlying pathognomonic processes predisposing to fibrotic lesions remain largely unknown. A deficiency in the ability of type 2 alveolar epithelial cell (AEC2) progenitors to regenerate and repair the epithelia has been proposed as a critical factor. In this issue of the JCI, Liang et al. identify a deficiency in the zinc transporter SLC39A8 (ZIP8) in AEC2s and in the subsequent activation of the sirtuin SIRT1 that predisposes to decreased AEC2 renewal capacity and enhanced lung fibrosis in both IPF and aging lungs. Interestingly, the authors demonstrate the efficacy of modulating dietary zinc levels, suggesting the need for clinical trials to evaluate the therapeutic potential of dietary supplementation and the development of pharmacological modulation of the Zn/ZIP8/SIRT1 axis for treatment.
虽然衰老和肺部损伤与特发性肺纤维化 (IPF) 的发展有关，但导致纤维病变的潜在特征性过程在很大程度上仍不清楚。有人提出，II 型肺泡上皮细胞 (AEC2) 祖细胞再生和修复上皮的能力不足是一个关键因素。在本期 JCI 中，Liang 等人发现 AEC2 中的锌转运蛋白 SLC39A8 (ZIP8) 以及随后的 SIRT1 沉默调节蛋白 1 (SIRT1) 的激活缺陷，导致 AEC2 更新能力下降，并增强了 IPF 和衰老肺中的肺纤维化。有趣的是，作者证明了调节膳食锌水平的有效性，这表明需要进行临床试验来评估膳食补充的治疗潜力，并开发针对 Zn/ZIP8/SIRT1 轴的药理学调节治疗。
