Cryptosporidium parvum regulates HCT-8 cell autophagy to facilitate survival via inhibiting miR-26a and promoting miR-30a expression.
Cryptosporidium parvum regulates HCT-8 cell autophagy to facilitate survival via inhibiting miR-26a and promoting miR-30a expression.
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小隐孢子虫通过抑制 miR-26a 和促进 miR-30a 表达调节 HCT-8 细胞自噬以促进存活
DOI：
10.1186/s13071-022-05606-y
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发表时间：
2022-12-15
影响因子：
3.2
通讯作者：
Li, Jianhua
中科院分区：
文献类型：
--
作者：
Jiang, Heng;Zhang, Xu;Li, Xin;Wang, Xiaocen;Zhang, Nan;Gong, Pengtao;Zhang, Xichen;Yu, Yanhui;Li, Jianhua
微小隐孢子虫是一种重要的人畜共患寄生虫，不仅给畜牧业造成经济损失，而且危害人类健康。由于缺乏有效的预防和治疗措施，因此了解其发病机制和生存机制具有重要意义。小的自噬是宿主细胞抗寄生虫感染的重要机制，通过microRNA和MAPK等关键调控因子介导。但C. parvum对自噬的影响未见报道。在这里，我们证明了C。parvum通过宿主细胞miR-26 a、miR-30 a、ERK信号传导和P38信号传导操纵自噬以使寄生虫存活。免疫印迹法检测C.以及用miR-26 a-模拟物、miR-30 a-模拟物、miR-26 a-模拟物或miR-30 a-抑制剂处理C.细小病毒感染采用qPCR方法检测miR-26 a、miR-30 a的表达及C.在HCT-8细胞中发现了细小病毒。此外，自噬体的积累，使用免疫荧光检查。Beclin 1和p62表达增加，而LC 3表达在0-8 h开始增加，12 h下降，然后再次增加。被细小病毒感染的细胞C. parvum抑制miR-26 a模拟物诱导的miR-26 a表达，但促进miR-30 a模拟物诱导的miR-30 a表达。抑制miR-30 a导致LC 3和Beclin 1的表达增加。然而，上调miR-26 a降低ERK/P38磷酸化，抑制ERK/P38信号促进Beclin 1和LC 3，同时降低p62表达。用miR-26 a模拟物、自噬诱导剂或ERK/P38信号传导抑制剂处理减少，但用自噬抑制剂或miR-30 a模拟物处理增加寄生虫数量。研究发现，C. parvum可以通过抑制miR-26 a和促进miR-30 a的表达来调节自噬，从而促进寄生虫的增殖。这些结果揭示了C. parvum与宿主细胞。在线版本包含补充材料，可通过10.1186/s13071-022-05606-y获得。
Cryptosporidium parvum is an important zoonotic parasite, which not only causes economic losses in animal husbandry but also harms human health. Due to the lack of effective measures for prevention and treatment, it is important to understand the pathogenesis and survival mechanism of C. parvum. Autophagy is an important mechanism of host cells against parasite infection through key regulatory factors such as microRNAs and MAPK pathways. However, the regulatory effect of C. parvum on autophagy has not been reported. Here, we demonstrated that C. parvum manipulated autophagy through host cellular miR-26a, miR-30a, ERK signaling and P38 signaling for parasite survival. The expression of Beclin1, p62, LC3, ERK and P38 was detected using western blotting in HCT-8 cells infected with C. parvum as well as treated with miR-26a-mimic, miR-30a-mimic, miR-26a-mimic or miR-30a-inhibitor post C. parvum infection. The qPCR was used to detect the expression of miR-26a and miR-30a and the number of C. parvum in HCT-8 cells. Besides, the accumulation of autophagosomes was examined using immunofluorescence. The expression of Beclin1 and p62 was increased, whereas LC3 expression was increased initially at 0–8 h but decreased at 12 h and then increased again in C. parvum-infected cells. C. parvum inhibited miR-26a-mimic-induced miR-26a but promoted miR-30a-mimic-induced miR-30a expression. Suppressing miR-30a resulted in increased expression of LC3 and Beclin1. However, upregulation of miR-26a reduced ERK/P38 phosphorylation, and inhibiting ERK/P38 signaling promoted Beclin1 and LC3 while reducing p62 expression. Treatment with miR-26a-mimic, autophagy inducer or ERK/P38 signaling inhibitors reduced but treatment with autophagy inhibitor or miR-30a-mimic increased parasite number. The study found that C. parvum could regulate autophagy by inhibiting miR-26a and promoting miR-30a expression to facilitate the proliferation of parasites. These results revealed a new mechanism for the interaction of C. parvum with host cells. The online version contains supplementary material available at 10.1186/s13071-022-05606-y.
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影响因子：
5.1
作者：
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通讯作者：
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影响因子：
5.1
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3.4
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