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Differential Expression of microRNAs in Thymic Epithelial Cells from Trypanosoma cruzi Acutely Infected Mice: Putative Role in Thymic Atrophy.

Linhares-Lacerda L, Palu CC, Ribeiro-Alves M, Paredes BD, Morrot A, Garcia-Silva MR, Cayota A, Savino W - Front Immunol (2015)

Bottom Line: Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation.In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death.Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease.

View Article: PubMed Central - PubMed

Affiliation: Laboratory on Thymus Research, Institute Oswaldo Cruz, Oswaldo Cruz Foundation , Rio de Janeiro , Brazil.

ABSTRACT
A common feature seen in acute infections is a severe atrophy of the thymus. This occurs in the murine model of acute Chagas disease. Moreover, in thymuses from Trypanosoma cruzi acutely infected mice, thymocytes exhibit an increase in the density of fibronectin and laminin integrin-type receptors, with an increase in migratory response ex vivo. Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation. To date, the consequences of molecular changes promoted by parasite infection upon thymus have not been elucidated. Considering the importance of microRNA for gene expression regulation, 85 microRNAs (mRNAs) were analyzed in TEC from T. cruzi acutely infected mice. The infection significantly modulated 29 miRNAs and modulation of 9 was also dependent whether TEC sorted out from the thymus exhibited cortical or medullary phenotype. In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death. Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease.

No MeSH data available.


Related in: MedlinePlus

Putative enriched biological processes modulated by TEC miRNA following Trypanosoma cruzi infection. The putative mRNA targets for the 29 miRNAs that were differentially expressed due to infection are consistently involved in a long list of biological processes. Here, we show the most relevant processes in the context of cell death (blue), adhesion (green), and migration (red). The full length of the bars represent the total putative target mRNAs known to be involved in this process, in opposition to the colored bar inside, that represents the expected mRNA number. On the right side of each bar, there is the adjusted p-value indicating that the enrichment of those events is not by chance.
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Figure 4: Putative enriched biological processes modulated by TEC miRNA following Trypanosoma cruzi infection. The putative mRNA targets for the 29 miRNAs that were differentially expressed due to infection are consistently involved in a long list of biological processes. Here, we show the most relevant processes in the context of cell death (blue), adhesion (green), and migration (red). The full length of the bars represent the total putative target mRNAs known to be involved in this process, in opposition to the colored bar inside, that represents the expected mRNA number. On the right side of each bar, there is the adjusted p-value indicating that the enrichment of those events is not by chance.

Mentions: To approach the putative roles of these miRNAs, we identified potential targets using available algorithms. Yet, these algorithms usually predict hundreds of potential target genes for a single miRNA and often generate false-positive candidates. In order to reduce such a high number of theoretical targets, and to make a more reliable prediction, we applied five different algorithms, and considered as potential targets only those genes predicted by at least three of these algorithms. The results from miRNAs predicted targets analysis were then combined with GO-term enrichment analysis to identified biological processes over represented among the list of target genes, so that to identify miRNA associated biological functions. Significant enrichment of predicted targets revealed cell adhesion, cell migration, and cell death among others biological processes (Figure 4).


Differential Expression of microRNAs in Thymic Epithelial Cells from Trypanosoma cruzi Acutely Infected Mice: Putative Role in Thymic Atrophy.

Linhares-Lacerda L, Palu CC, Ribeiro-Alves M, Paredes BD, Morrot A, Garcia-Silva MR, Cayota A, Savino W - Front Immunol (2015)

Putative enriched biological processes modulated by TEC miRNA following Trypanosoma cruzi infection. The putative mRNA targets for the 29 miRNAs that were differentially expressed due to infection are consistently involved in a long list of biological processes. Here, we show the most relevant processes in the context of cell death (blue), adhesion (green), and migration (red). The full length of the bars represent the total putative target mRNAs known to be involved in this process, in opposition to the colored bar inside, that represents the expected mRNA number. On the right side of each bar, there is the adjusted p-value indicating that the enrichment of those events is not by chance.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543887&req=5

Figure 4: Putative enriched biological processes modulated by TEC miRNA following Trypanosoma cruzi infection. The putative mRNA targets for the 29 miRNAs that were differentially expressed due to infection are consistently involved in a long list of biological processes. Here, we show the most relevant processes in the context of cell death (blue), adhesion (green), and migration (red). The full length of the bars represent the total putative target mRNAs known to be involved in this process, in opposition to the colored bar inside, that represents the expected mRNA number. On the right side of each bar, there is the adjusted p-value indicating that the enrichment of those events is not by chance.
Mentions: To approach the putative roles of these miRNAs, we identified potential targets using available algorithms. Yet, these algorithms usually predict hundreds of potential target genes for a single miRNA and often generate false-positive candidates. In order to reduce such a high number of theoretical targets, and to make a more reliable prediction, we applied five different algorithms, and considered as potential targets only those genes predicted by at least three of these algorithms. The results from miRNAs predicted targets analysis were then combined with GO-term enrichment analysis to identified biological processes over represented among the list of target genes, so that to identify miRNA associated biological functions. Significant enrichment of predicted targets revealed cell adhesion, cell migration, and cell death among others biological processes (Figure 4).

Bottom Line: Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation.In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death.Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease.

View Article: PubMed Central - PubMed

Affiliation: Laboratory on Thymus Research, Institute Oswaldo Cruz, Oswaldo Cruz Foundation , Rio de Janeiro , Brazil.

ABSTRACT
A common feature seen in acute infections is a severe atrophy of the thymus. This occurs in the murine model of acute Chagas disease. Moreover, in thymuses from Trypanosoma cruzi acutely infected mice, thymocytes exhibit an increase in the density of fibronectin and laminin integrin-type receptors, with an increase in migratory response ex vivo. Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation. To date, the consequences of molecular changes promoted by parasite infection upon thymus have not been elucidated. Considering the importance of microRNA for gene expression regulation, 85 microRNAs (mRNAs) were analyzed in TEC from T. cruzi acutely infected mice. The infection significantly modulated 29 miRNAs and modulation of 9 was also dependent whether TEC sorted out from the thymus exhibited cortical or medullary phenotype. In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death. Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease.

No MeSH data available.


Related in: MedlinePlus