Abstract：
In a mouse model of influenza pneumonia, we previously documented that proliferating alveolar type II (AT2) cells are the major stem cells involved in early lung recovery. Profiling of microRNAs revealed significant dysregulation of specific ones, including miR-21 and miR-99a. Moreover, miR-145 is known to exhibit antagonism to miR-21. This follow-up study investigated the roles of microRNAs miR-21, miR-99a, and miR-145 in the murine pulmonary regenerative process and inflammation during influenza pneumonia. Inhibition of miR-21 resulted in severe morbidity, and in significantly decreased proliferating AT2 cells due to impaired transition from innate to adaptive immune responses. Knockdown of miR-99a culminated in moderate morbidity, with a significant increase in proliferating AT2 cells that may be linked to PTEN downregulation. In contrast, miR-145 antagonism did not impact morbidity nor the proliferating AT2 cell population, and was associated with downregulation of TNF-alpha, IL1-beta, YM1, and LY6G. Hence, a complex interplay exists between expression of specific miRNAs, lung regeneration, and inflammation during recovery from influenza pneumonia. Inhibition of miR-21 and miR-99a (but not miR-145) can lead to deleterious cellular and molecular effects on pulmonary repair and inflammatory processes during influenza pneumonia.
摘要：
在流感肺炎的小鼠模型中，我们先前证实,增殖的肺泡II型(AT2)细胞是参与早期肺恢复的主要干细胞.对microRNA的分析揭示了特定RNA的显着失调，包括miR-21和miR-99a。此外，已知miR-145表现出对miR-21的拮抗作用。这项后续研究调查了miR-21，miR-99a，和miR-145在流感肺炎期间小鼠肺再生过程和炎症中的作用。抑制miR-21导致严重的发病率，并且由于从先天免疫应答到适应性免疫应答的过渡受损，增殖AT2细胞显着减少。miR-99a的敲低导致中等发病率，与增殖的AT2细胞显着增加，这可能与PTEN下调有关。相比之下,miR-145拮抗作用不影响发病率或增殖的AT2细胞群，并与TNF-α的下调有关，IL1-beta,YM1和LY6G。因此，特定miRNA的表达之间存在复杂的相互作用，肺再生，流感肺炎恢复期间的炎症。抑制miR-21和miR-99a(但不抑制miR-145)可导致对流感肺炎期间的肺修复和炎症过程的有害细胞和分子效应。
