Ninjurin1 Plays a Crucial Role in Pulmonary Fibrosis by Promoting Interaction between Macrophages and Alveolar Epithelial Cells.
Ninjurin1 Plays a Crucial Role in Pulmonary Fibrosis by Promoting Interaction between Macrophages and Alveolar Epithelial Cells.
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DOI：
10.1038/s41598-018-35997-x
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发表时间：
2018-12-03
影响因子：
4.6
通讯作者：
Oh SH
中科院分区：
文献类型：
--
作者：
Choi S;Woo JK;Jang YS;Kang JH;Hwang JI;Seong JK;Yoon YS;Oh SH
跨膜神经损伤诱导蛋白 1（Ninjurin1 或 Ninj1）与炎症性疾病的进展有关。在本研究中，我们旨在研究 Ninj1 在肺纤维化中的新功能。我们发现，在特发性肺纤维化患者以及博来霉素诱导的肺纤维化小鼠的肺标本中，Ninj1 的表达在患者队列中上调。此外，与 WT 小鼠相比，注射 BLM 的 Ninj1 KO 小鼠表现出轻度纤维化表型。因此，我们推测Ninj1在肺纤维化的发生过程中发挥重要作用。我们发现 BLM 处理的巨噬细胞和肺泡上皮细胞 (AEC) 中 Ninj1 表达增加。有趣的是，与 BLM 处理的 AEC 结合的巨噬细胞被激活。然而，当 AEC 或巨噬细胞中的 Ninj1 表达受到抑制时，巨噬细胞与 AEC 的接触依赖性激活就会减弱。此外，将重组小鼠 Ninj11-50 引入巨噬细胞会引发炎症反应，但不会刺激 Ninj1 缺陷的巨噬细胞。总之，我们认为 Ninj1 可能通过增强与因损伤诱导刺激而导致 Ninj1 表达升高的 AEC 的相互作用，从而有助于巨噬细胞的激活。因此，Ninj1可能通过增强巨噬细胞的炎症反应参与肺纤维化的发生。
The transmembrane nerve injury-induced protein 1 (Ninjurin1 or Ninj1) is involved in progressing inflammatory diseases. In this study, we aimed to investigate a novel function of Ninj1 in pulmonary fibrosis. We found that the expression of Ninj1 in a patient cohort was upregulated in the lung specimens of idiopathic pulmonary fibrosis patients as well as mice with bleomycin-induced pulmonary fibrosis. In addition, the BLM-injected Ninj1 KO mice exhibited a mild fibrotic phenotype, as compared to WT mice. Therefore, we hypothesized that Ninj1 would play an important role in the development of pulmonary fibrosis. We discovered that Ninj1 expression increased in BLM-treated macrophages and alveolar epithelial cells (AECs). Interestingly, macrophages bound to BLM-treated AECs were activated. However, when Ninj1 expression was suppressed in either of AECs or macrophages, contact-dependent activation of macrophages with AECs was diminished. In addition, introduction of recombinant mouse Ninj11–50 to macrophages triggered an inflammatory response, but did not stimulate Ninj1-deficient macrophages. In conclusion, we propose that Ninj1 may contribute to activation of macrophages by enhancing interaction with AECs having elevated Ninj1 expression due to injury-inducing stimuli. Consequently, Ninj1 may be involved in the development of pulmonary fibrosis by enhancing inflammatory response of macrophages.