دورية أكاديمية
Toxoplasma gondii infection regulates apoptosis of host cells via miR-185/ARAF axis.
العنوان: | Toxoplasma gondii infection regulates apoptosis of host cells via miR-185/ARAF axis. |
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المؤلفون: | Su D; College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, People's Republic of China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, 225009, People's Republic of China.; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, People's Republic of China., Zhu S; College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, People's Republic of China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, 225009, People's Republic of China.; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, People's Republic of China., Hou Z; College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, People's Republic of China. zfhou@yzu.edu.cn.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, 225009, People's Republic of China. zfhou@yzu.edu.cn.; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, People's Republic of China. zfhou@yzu.edu.cn., Hao F; Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, 225300, People's Republic of China., Xu K; College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, People's Republic of China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, 225009, People's Republic of China.; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, People's Republic of China., Xu F; College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, People's Republic of China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, 225009, People's Republic of China.; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, People's Republic of China., Zhu Y; College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, People's Republic of China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, 225009, People's Republic of China.; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, People's Republic of China., Liu D; College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, People's Republic of China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, 225009, People's Republic of China.; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, People's Republic of China., Xu J; College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, People's Republic of China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, 225009, People's Republic of China.; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, People's Republic of China., Tao J; College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, People's Republic of China. yzjptao@126.com.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, 225009, People's Republic of China. yzjptao@126.com.; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, People's Republic of China. yzjptao@126.com. |
المصدر: | Parasites & vectors [Parasit Vectors] 2023 Oct 19; Vol. 16 (1), pp. 371. Date of Electronic Publication: 2023 Oct 19. |
نوع المنشور: | Evaluation Study; Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101462774 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-3305 (Electronic) Linking ISSN: 17563305 NLM ISO Abbreviation: Parasit Vectors Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central |
مواضيع طبية MeSH: | MicroRNAs*/genetics , MicroRNAs*/metabolism , Swine Diseases*/genetics , Swine Diseases*/metabolism , Swine Diseases*/parasitology , Toxoplasma* , Toxoplasmosis*/genetics , Toxoplasmosis*/metabolism , Proto-Oncogene Proteins A-raf*/genetics , Proto-Oncogene Proteins A-raf*/metabolism, Animals ; Mice ; Apoptosis/genetics ; Apoptosis/immunology ; Caspase 3 ; Cells, Cultured ; Luciferases ; Swine/genetics ; Swine/metabolism ; Swine/parasitology |
مستخلص: | Background: Toxoplasmosis is a zoonosis with a worldwide presence that is caused by the intracellular parasite Toxoplasma gondii. Active regulation of apoptosis is an important immune mechanism by which host cells resist the growth of T. gondii or avoid excessive pathological damage induced by this parasite. Previous studies found that upregulated expression of microRNA-185 (miR-185) during T. gondii infection has a potential role in regulating the expression of the ARAF gene, which is reported to be associated with cell proliferation and apoptosis. Methods: The expression levels of miR-185 and the ARAF gene were evaluated by qPCR and Western blot, respectively, in mice tissues, porcine kidney epithelial cells (PK-15) and porcine alveolar macrophages (3D4/21) following infection with the T. gondii ToxoDB#9 and RH strains. The dual luciferase reporter assay was then used to verify the relationship between miR-185 and ARAF targets in PK-15 cells. PK-15 and 3D4/21 cell lines with stable knockout of the ARAF gene were established by CRISPR, and then the apoptosis rates of the cells following T. gondii infection were detected using cell flow cytometry assays. Simultaneously, the activities of cleaved caspase-3, as a key apoptosis executive protein, were detected by Western blot to evaluate the apoptosis levels of cells. Results: Infection with both the T. gondii ToxoDB#9 and RH strains induced an increased expression of miR-185 and a decreased expression of ARAF in mice tissues, PK-15 and 3D4/21 cells. MiR-185 mimic transfections showed a significantly negative correlation in expression levels between miR-185 and the ARAF gene. The dual luciferase reporter assay confirmed that ARAF was a target of miR-185. Functional investigation revealed that T. gondii infection induced the apoptosis of PK-15 and 3D4/21 cells, which could be inhibited by ARAF knockout or overexpression of miR-185. The expression levels of cleaved caspase-3 protein were significantly lower in cells with ARAF knockout than in normal cells, which were consistent with the results of the cell flow cytometry assays. Conclusions: Toxoplasma gondii infection could lead to the upregulation of miR-185 and the downregulation of ARAF, which was not related to the strain of T. gondii and the host cells. Toxoplasma gondii infection could regulate the apoptosis of host cells via the miR-185/ARAF axis, which represents an additional strategy used by T. gondii to counteract host-cell apoptosis in order to maintain survival and reproduce in the host cells. (© 2023. BioMed Central Ltd., part of Springer Nature.) |
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معلومات مُعتمدة: | 32002303 National Natural Science Foundation of China; 2020M671615 China Postdoctoral Science Foundation; BK20190885 Basic Research Program of Jiangsu Province; 6 International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions; RCPY201929 Taizhou Project of Scientific Research for Talent Cultivation; X20220678 Undergraduate Scientific Research Innovation Funds of Yangzhou University |
فهرسة مساهمة: | Keywords: ARAF; Apoptosis; Host cell; Regulation; Toxoplasma gondii; miR-185 |
المشرفين على المادة: | EC 3.4.22.- (Caspase 3) EC 1.13.12.- (Luciferases) 0 (MicroRNAs) 0 (Mirn185 microRNA, mouse) EC 2.7.11.1 (Proto-Oncogene Proteins A-raf) |
تواريخ الأحداث: | Date Created: 20231020 Date Completed: 20231101 Latest Revision: 20231121 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC10585723 |
DOI: | 10.1186/s13071-023-05991-y |
PMID: | 37858158 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1756-3305 |
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DOI: | 10.1186/s13071-023-05991-y |