Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica
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Published:2023-03-21
Issue:3
Volume:11
Page:796
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ISSN:2076-2607
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Container-title:Microorganisms
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language:en
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Short-container-title:Microorganisms
Author:
Zhao Ruyu1, Tang Xiaoxue1, Lin Huiyao1, Xing Chen1, Xu Na1, Dai Bingxin1, Wang Pingping1, Shao Wei1ORCID, Liu Miao1, Shen Jijia1, Deng Shengqun1ORCID, Ren Cuiping1
Affiliation:
1. Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, Anhui Key Laboratory of Zoonosis of High Institution, Laboratory of Tropical and Parasitic Diseases Control, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
Abstract
Long noncoding RNAs (lncRNAs) can regulate key genes and pathways in liver disease development. Moreover, macrophages are speculated to play an important role in regulating granulomatous inflammation during schistosomiasis. However, the role of lncRNAs in the formation of liver granulomas by influencing the polarization of macrophages in Schistosoma japonicum infection is unclear. Our study aimed to determine whether lncRNAs can play a role in S. japonicum-induced hepatic egg granulomas and elucidate their effect on macrophages. We established S. japonicum infection models and screened the target lncRNA Gm16685 highly expressed in schistosomiasis mice using high-throughput sequencing. Hematoxylin and eosin staining revealed that the knockdown of Gm16685 reduced the area of egg granulomas. Moreover, M1 macrophage factor genes were significantly downregulated in Gm16685 knockdown livers. Meanwhile, M2 macrophage factor genes were significantly upregulated, which was consistent with the protein detection results. Hepatocytes, hepatic stellate cells, and macrophages were isolated from mouse models infected with S. japonicum, with Gm16685 being significantly upregulated in macrophages. Moreover, the knockdown of Gm16685 in RAW264.7 cells revealed similar results to in liver tissue. RNA fluorescence in situ hybridization (FISH) and nucleocytoplasmic separation experiments revealed that Gm16685 was predominantly localized in the cytoplasm of cells. We found that miR-205-5p was upregulated after Gm16685 was knocked down. After overexpression of miR-205-5p, the expression of Gm16685 and inflammatory factors was significantly downregulated. These results indicate that Gm16685 can participate in the pathogenesis of hepatic disease in schistosomiasis and promote M1 macrophage polarization by regulating miR-205-5p. Thus, our study may provide a new target for schistosomiasis japonica treatment.
Funder
National Natural Science Foundation of China Scientific Research of BSKY from Anhui Medical University
Subject
Virology,Microbiology (medical),Microbiology
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