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Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica
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 influen...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058064/ https://www.ncbi.nlm.nih.gov/pubmed/36985369 http://dx.doi.org/10.3390/microorganisms11030796 |
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author | Zhao, Ruyu Tang, Xiaoxue Lin, Huiyao Xing, Chen Xu, Na Dai, Bingxin Wang, Pingping Shao, Wei Liu, Miao Shen, Jijia Deng, Shengqun Ren, Cuiping |
author_facet | Zhao, Ruyu Tang, Xiaoxue Lin, Huiyao Xing, Chen Xu, Na Dai, Bingxin Wang, Pingping Shao, Wei Liu, Miao Shen, Jijia Deng, Shengqun Ren, Cuiping |
author_sort | Zhao, Ruyu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10058064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100580642023-03-30 Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica Zhao, Ruyu Tang, Xiaoxue Lin, Huiyao Xing, Chen Xu, Na Dai, Bingxin Wang, Pingping Shao, Wei Liu, Miao Shen, Jijia Deng, Shengqun Ren, Cuiping Microorganisms Article 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. MDPI 2023-03-21 /pmc/articles/PMC10058064/ /pubmed/36985369 http://dx.doi.org/10.3390/microorganisms11030796 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhao, Ruyu Tang, Xiaoxue Lin, Huiyao Xing, Chen Xu, Na Dai, Bingxin Wang, Pingping Shao, Wei Liu, Miao Shen, Jijia Deng, Shengqun Ren, Cuiping Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica |
title | Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica |
title_full | Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica |
title_fullStr | Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica |
title_full_unstemmed | Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica |
title_short | Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica |
title_sort | knocking down gm16685 decreases liver granuloma in murine schistosomiasis japonica |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058064/ https://www.ncbi.nlm.nih.gov/pubmed/36985369 http://dx.doi.org/10.3390/microorganisms11030796 |
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