Colin Waldo Marisa Denisse, Quintero-Millán Xochipilzihuitl, Negrete-García Maria Cristina, Ruiz Víctor, Sommer Bettina, Romero-Rodríguez Dámaris P, Montes-Martínez Eduardo
Molecular Biology Laboratory, Department of Research in Pulmonary Fibrosis, National Institute of Respiratory Diseases "Ismael Cosío Villegas", Calzada de Tlalpan 4502, Col. Sección XVI, Mexico City 14080, Mexico.
Bronchial Hyperreactivity Research Department, National Institute of Respiratory Diseases "Ismael Cosío Villegas", Calzada de Tlalpan 4502, Col. Sección XVI, Mexico City 14080, Mexico.
Curr Issues Mol Biol. 2024 Dec 4;46(12):13746-13766. doi: 10.3390/cimb46120821.
Idiopathic pulmonary fibrosis (IPF) is a chronic, deathly disease with no recognized effective cure as yet. Furthermore, its diagnosis and differentiation from other diffuse interstitial diseases remain a challenge. Circulating miRNAs have been measured in IPF and have proven to be an adequate option as biomarkers for this disease. These miRNAs, released into the circulation outside the cell through exosomes and proteins, play a crucial role in the pathogenic pathways and mechanisms involved in IPF development. This review focuses on the serum/plasma miRNAs reported in IPF that have been validated by real-time PCR and the published evidence regarding the fibrotic process. First, we describe the mechanisms by which miRNAs travel through the circulation (contained in exosomes and bound to proteins), as well as the mechanism by which miRNAs perform their function within the cell. Subsequently, we summarize the evidence concerning miRNAs reported in serum/plasma, where we find contradictory functions in some miRNAs (dual functions in IPF) when comparing the findings in vitro vs. in vivo. The most relevant finding, for instance, the levels of miRNAs let-7d and miR-21 reported in the serum/plasma in IPF, correspond to those found in studies in lung fibroblasts and the murine bleomycin model, reinforcing the usefulness of these miRNAs as future biomarkers in IPF.
特发性肺纤维化（IPF）是一种慢性致命性疾病，目前尚无公认的有效治愈方法。此外，其诊断以及与其他弥漫性间质性疾病的鉴别仍然是一项挑战。在IPF患者中已检测到循环中的微小RNA（miRNA），并且已证明其作为该疾病生物标志物是一种合适的选择。这些通过外泌体和蛋白质释放到细胞外循环中的miRNA，在IPF发生发展的致病途径和机制中起关键作用。本综述聚焦于IPF中已通过实时聚合酶链反应验证的血清/血浆miRNA以及有关纤维化过程的已发表证据。首先，我们描述miRNA在循环中运输的机制（包含在外泌体中并与蛋白质结合），以及miRNA在细胞内发挥功能的机制。随后，我们总结血清/血浆中报道的miRNA的相关证据，在比较体外和体内研究结果时，我们发现一些miRNA存在相互矛盾的功能（在IPF中具有双重功能）。例如，最相关的发现是IPF血清/血浆中报道的miRNA let-7d和miR-21的水平，与在肺成纤维细胞和小鼠博来霉素模型研究中发现的水平一致，这增强了这些miRNA作为IPF未来生物标志物的实用性。
