Wu Yuting, Xu Hong, Li Yongqiang, Huang Dongwei, Chen Lu, Hu Yahui, Li Li, Zhang Deming, Huang Wenjie
Department of Geriatric Respiratory Medicine, General Hospital of Southern Theater Command, PLA, Guangzhou, Guangdong 510010, P.R. China.
Respiratory Center of PLA, General Hospital of Southern Theater Command, PLA, Guangzhou, Guangdong 510010, P.R. China.
Exp Ther Med. 2019 Jul;18(1):139-146. doi: 10.3892/etm.2019.7569. Epub 2019 May 10.
Autophagy serves a pivotal role in host defense during fungal infections, and the contribution by toll-like receptor 2 (TLR2) has been well demonstrated. It has been reported that microRNA-344a-1-3p (miR-344a-1-3p) can directly target TLR2. However, the expression of TLR2 significantly decreases during infection. Therefore, the specific role of miR-344a-1-3p in the host defense against infection remains to be elucidated. In the present study, infection increased the expression of TLR2 and induced autophagy, which was indicated by increasing expression levels of autophagy-related protein 5 (ATG5), Beclin-1, light chain 3 (LC3)-1 and LC3-II, as measured by western blot analysis, and an increased number of GFP-LC3 puncta, as measured by fluorescence. Following transfection with miR-344a-1-3p mimics and/or TLR2, miR-344b-1-3p significantly inhibited the expression of TLR2, Beclin-1, ATG5, LC3-I and LC3-II, whereas the overexpression of TLR2 significantly attenuated the inhibitory effect on autophagy by miR-344b-1-3p. Collectively, these findings demonstrate that can be controlled by the induction of autophagy following de-repression of the expression of TLR2, mediated by miR-344a-1-3p.
自噬在真菌感染期间的宿主防御中起关键作用,并且Toll样受体2(TLR2)的作用已得到充分证实。据报道,微小RNA-344a-1-3p(miR-344a-1-3p)可直接靶向TLR2。然而,在感染期间TLR2的表达显著降低。因此,miR-344a-1-3p在宿主抵抗感染的防御中的具体作用仍有待阐明。在本研究中,感染增加了TLR2的表达并诱导了自噬,这通过蛋白质印迹分析测定的自噬相关蛋白5(ATG5)、Beclin-1、轻链3(LC3)-I和LC3-II表达水平的增加以及通过荧光测定的GFP-LC3斑点数量的增加来表明。用miR-344a-1-3p模拟物和/或TLR2转染后,miR-344b-1-3p显著抑制TLR2、Beclin-1、ATG5、LC3-I和LC3-II的表达,而TLR2的过表达显著减弱了miR-344b-1-3p对自噬的抑制作用。总的来说,这些发现表明, 可通过miR-344a-1-3p介导的TLR2表达去抑制后诱导自噬来控制。 (注:原文中“ infection increased...”和“Collectively, these findings demonstrate that can be controlled...”两处有缺失信息未明确写出)