Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, College of Medicine, Pennsylvania State University, Hershey, PA, United States.
Department of Obstetrics and Gynecology, College of Medicine, Pennsylvania State University, Hershey, PA, United States.
Front Immunol. 2019 Jul 10;10:1514. doi: 10.3389/fimmu.2019.01514. eCollection 2019.
Pulmonary surfactant protein A (SP-A) plays an important role in surfactant metabolism and lung innate immunity. In humans there are two proteins, SP-A1 and SP-A2, encoded by and , respectively, which are produced by the alveolar type II cells (T2C). We sought to investigate the differential influence of SP-A1 and SP-A2 in T2C miRNome under oxidative stress (OxS). SP-A knock out (KO) and hTG male and female mice expressing SP-A1 or SP-A2 as well as gonadectomized (Gx) mice were exposed to O-induced oxidative stress (OxS) or filtered air (FA). Expression of miRNAs and mRNAs was measured in the T2C of experimental animals. (a) In SP-A1 males after normalizing to KO males, significant changes were observed in the miRNome in terms of sex-OxS effects, with 24 miRNAs being differentially expressed under OxS. (b) The mRNA targets of the dysregulated miRNAs included , and . We validated the expression levels of these transcripts, and observed that the mRNA levels of all of these targets were unaffected in SP-A1 T2C but six of these were significantly upregulated in the KO (except that was downregulated). (c) Gondadectomy had a major effect on the expression of miRNAs and in three of the mRNA targets (, and ). was upregulated in KO regardless of Gx. (d) The targets of the significantly changed miRNAs are involved in several pathways including signaling pathway, cell cycle, anti-apoptosis, and other. In conclusion, in response to OxS, SP-A1 and male hormones appear to have a major effect in the T2C miRNome.
肺表面活性物质蛋白 A (SP-A) 在表面活性物质代谢和肺固有免疫中发挥重要作用。在人类中，有两种蛋白质，SP-A1 和 SP-A2，分别由 和 编码，由肺泡 II 型细胞 (T2C) 产生。我们试图研究 SP-A1 和 SP-A2 在 T2C 微小 RNA 组中的差异影响在氧化应激 (OxS) 下。SP-A 敲除 (KO) 和表达 SP-A1 或 SP-A2 的 hTG 雄性和雌性小鼠以及性腺切除 (Gx) 小鼠暴露于 O 诱导的氧化应激 (OxS) 或过滤空气 (FA)。在实验动物的 T2C 中测量微小 RNA 和 mRNA 的表达。(a) 在正常化到 KO 雄性的 SP-A1 雄性中，miRNome 中观察到性别-OxS 效应的显著变化，有 24 个微小 RNA 在 OxS 下差异表达。(b) 失调微小 RNA 的 mRNA 靶标包括 、 和 。我们验证了这些转录物的表达水平，并观察到这些靶标的所有 mRNA 水平在 SP-A1 T2C 中不受影响，但在 KO 中六个靶标显著上调（除 下调外）。(c) 性腺切除术对微小 RNA 和三个 mRNA 靶标（ 、 和 ）的表达有重大影响。在 KO 中，无论 Gx 如何， 均上调。(d) 显著变化的微小 RNA 的靶标参与几个途径，包括 信号通路、细胞周期、抗凋亡和其他途径。总之，对 OxS 的反应中，SP-A1 和雄性激素似乎对 T2C 微小 RNA 组有重大影响。
