| Autor: |
Katherine-Sofia Candray-Medina, Yu Nakagama, Masamichi Ito, Shun Nakagama, Evariste Tshibangu-Kabamba, Norihiko Takeda, Yuki Sugiura, Yuko Nitahara, Yu Michimuko-Nagahara, Natsuko Kaku, Yoko Onizuka, Carmen-Elena Arias, Maricela Mejia, Karla Alas, Susana Peña, Yasuhiro Maejima, Issei Komuro, Junko Nakajima-Shimada, Yasutoshi Kido |
| Rok vydání: |
2023 |
| DOI: |
10.1101/2023.02.27.530371 |
| Popis: |
Chagas disease can lead to life-threatening cardiac manifestations that occur more frequently in geographic areas more prevalent with the TcI/II circulating genetic strains. To elucidate the differential transcriptomic signatures of the cardiomyocyte resulting from infection with TcI/II or TcVIT. cruzistrains and explore their relationships with pathogenesis, HL-1 rodent cardiomyocytes were infected with TcI/II or TcVIT. cruzitrypomastigotes. RNA was isolated serially post-infection for microarray analysis. Enrichment analyses of differentially expressed genes (fold-change ≥2 or ≤ 0.5) highlighted the over-represented biological pathways. We found that Oxidative stress-related GO terms, ‘Hypertrophy model’, ‘Apoptosis’, and ‘MAPK signaling’ pathways (all with pImportanceChagas disease affects more than 6 million people worldwide. One-third of those chronically infected will develop the life-threatening condition Chagas Cardiomyopathy (CCM).Trypanosoma cruzi (T. cruzi), grouped based on their genetic variability into six discrete typing units (DTU), are associated with DTU-specific clinical phenotypes. The diverse genetic make-up of parasite virulence factors shall evoke unique host defense responses of variable magnitude, collectively affecting the phenotypic expression of CCM. To address this, we performed a transcriptome analysis of cardiomyocytes infected with three differentT. cruzistrains each belonging to a different DTU. As a result, we were able to point out dysregulation in nitrogen metabolic processes, Glutathione, and one-carbon metabolism pathways as main features in the host response against cardiomyopathy-proneT. cruzistrains. Further research on these pathways could serve not only in the lookout for progression biomarkers but also in the lead toward the discovery of new therapeutic targets. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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