Lu Wenying, Eapen Mathew Suji, Singhera Gurpreet Kaur, Markos James, Haug Greg, Chia Collin, Larby Josie, Brake Samuel James, Westall Glen P, Jaffar Jade, Kalidhindi Rama Satyanarayana Raju, Fonseka Nimesha De, Sathish Venkatachalem, Hackett Tillie L, Sohal Sukhwinder Singh
Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.
National Health and Medical Research Council (NHMRC) Centre of Research Excellence (CRE) in Pulmonary Fibrosis, Respiratory Medicine and Sleep Unit, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
J Clin Med. 2022 Jan 31;11(3):777. doi: 10.3390/jcm11030777.
We previously reported higher ACE2 levels in smokers and patients with COPD. The current study investigates if patients with interstitial lung diseases (ILDs) such as IPF and LAM have elevated ACE2, TMPRSS2, and Furin levels, increasing their risk for SARS-CoV-2 infection and development of COVID-19. Surgically resected lung tissue from IPF, LAM patients, and healthy controls (HC) was immunostained for ACE2, TMPRSS2, and Furin. Percentage ACE2, TMPRSS2, and Furin expression was measured in small airway epithelium (SAE) and alveolar areas using computer-assisted Image-Pro Plus 7.0 software. IPF and LAM tissue was also immunostained for myofibroblast marker α-smooth muscle actin (α-SMA) and growth factor transforming growth factor beta1 (TGF-β1). Compared to HC, ACE2, TMPRSS2 and Furin expression were significantly upregulated in the SAE of IPF ( < 0.01) and LAM ( < 0.001) patients, and in the alveolar areas of IPF ( < 0.001) and LAM ( < 0.01). There was a significant positive correlation between smoking history and ACE2 expression in the IPF cohort for SAE (r = 0.812, < 0.05) and alveolar areas (r = 0.941, < 0.01). This, to our knowledge, is the first study to compare ACE2, TMPRSS2, and Furin expression in patients with IPF and LAM compared to HC. Descriptive images show that α-SMA and TGF-β1 increase in the IPF and LAM tissue. Our data suggests that patients with ILDs are at a higher risk of developing severe COVID-19 infection and post-COVID-19 interstitial pulmonary fibrosis. Growth factors secreted by the myofibroblasts, and surrounding tissue could further affect COVID-19 adhesion proteins/cofactors and post-COVID-19 interstitial pulmonary fibrosis. Smoking seems to be the major driving factor in patients with IPF.
我们之前报道过吸烟者和慢性阻塞性肺疾病（COPD）患者的血管紧张素转换酶2（ACE2）水平较高。本研究调查了特发性肺纤维化（IPF）和淋巴管肌瘤病（LAM）等间质性肺疾病（ILD）患者的ACE2、跨膜丝氨酸蛋白酶2（TMPRSS2）和弗林蛋白酶水平是否升高，从而增加他们感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）和患2019冠状病毒病（COVID-19）的风险。对IPF、LAM患者以及健康对照（HC）手术切除的肺组织进行ACE2、TMPRSS2和弗林蛋白酶免疫染色。使用计算机辅助的Image-Pro Plus 7.0软件在小气道上皮（SAE）和肺泡区域测量ACE2、TMPRSS2和弗林蛋白酶的表达百分比。IPF和LAM组织也进行肌成纤维细胞标志物α-平滑肌肌动蛋白（α-SMA）和生长因子转化生长因子β1（TGF-β1）的免疫染色。与HC相比，IPF患者（<0.01）和LAM患者（<0.001）的SAE以及IPF患者（<0.001）和LAM患者（<0.01）的肺泡区域中，ACE2、TMPRSS2和弗林蛋白酶的表达显著上调。在IPF队列中，吸烟史与SAE的ACE2表达之间存在显著正相关（r = 0.812，<0.05），与肺泡区域的ACE2表达之间也存在显著正相关（r = 0.941，<0.01）。据我们所知，这是第一项比较IPF和LAM患者与HC的ACE2、TMPRSS2和弗林蛋白酶表达的研究。描述性图像显示IPF和LAM组织中α-SMA和TGF-β1增加。我们的数据表明，ILD患者发生严重COVID-19感染和COVID-19后间质性肺纤维化的风险更高。肌成纤维细胞和周围组织分泌的生长因子可能会进一步影响COVID-19黏附蛋白/辅助因子以及COVID-19后间质性肺纤维化。吸烟似乎是IPF患者的主要驱动因素。
