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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

Theoretical relationship among the most recurrent miRNA, mRNA, and biological processes. The network of the 29 differentially expressed miRNAs and their targets is very complex. To illustrate this network, only molecules or processes related with at least 11 elements are shown. There are 17 miR differentially expressed due to infection (cyan) and their 58 putative targets (yellow), plus 18 biological processes related to it. Biological processes are identified by gene ontology (GO) tags, where blue represents cell death, red are cell adhesion, and green cell migration. The relationships are illustrated by the arrows.
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Figure 5: Theoretical relationship among the most recurrent miRNA, mRNA, and biological processes. The network of the 29 differentially expressed miRNAs and their targets is very complex. To illustrate this network, only molecules or processes related with at least 11 elements are shown. There are 17 miR differentially expressed due to infection (cyan) and their 58 putative targets (yellow), plus 18 biological processes related to it. Biological processes are identified by gene ontology (GO) tags, where blue represents cell death, red are cell adhesion, and green cell migration. The relationships are illustrated by the arrows.

Mentions: Given the lack of data regarding TEC molecular pathways during infection, we evaluated in silico potential interaction network between 29 differentially expressed miRNAs and the predicted targets related to cell death, cell migration, and cell adhesion (Table S1 in Supplementary Material). The complexity of the relationships is shown in Figure 5, where the elements shown were selected based on having the minimum of 11 relations. All 17 miRNAs have at least one putative target related to the negative regulation of extrinsic apoptotic signaling (GO:2001237), a process that was also related to 12 out of the 58 illustrated genes. Nevertheless, among the genes involved in cell death, only Bcl2l11 was exclusively related to positive regulation of cell death. These miRNAs could be targeting Serpine1, Tgfbr1, Vegfa, Igf1, Hgf, Snai2, Rffl, Map2k5, Itgav, and Sgms1 mRNAs, which are related to inhibition of apoptotic externals signals.


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)

Theoretical relationship among the most recurrent miRNA, mRNA, and biological processes. The network of the 29 differentially expressed miRNAs and their targets is very complex. To illustrate this network, only molecules or processes related with at least 11 elements are shown. There are 17 miR differentially expressed due to infection (cyan) and their 58 putative targets (yellow), plus 18 biological processes related to it. Biological processes are identified by gene ontology (GO) tags, where blue represents cell death, red are cell adhesion, and green cell migration. The relationships are illustrated by the arrows.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Theoretical relationship among the most recurrent miRNA, mRNA, and biological processes. The network of the 29 differentially expressed miRNAs and their targets is very complex. To illustrate this network, only molecules or processes related with at least 11 elements are shown. There are 17 miR differentially expressed due to infection (cyan) and their 58 putative targets (yellow), plus 18 biological processes related to it. Biological processes are identified by gene ontology (GO) tags, where blue represents cell death, red are cell adhesion, and green cell migration. The relationships are illustrated by the arrows.
Mentions: Given the lack of data regarding TEC molecular pathways during infection, we evaluated in silico potential interaction network between 29 differentially expressed miRNAs and the predicted targets related to cell death, cell migration, and cell adhesion (Table S1 in Supplementary Material). The complexity of the relationships is shown in Figure 5, where the elements shown were selected based on having the minimum of 11 relations. All 17 miRNAs have at least one putative target related to the negative regulation of extrinsic apoptotic signaling (GO:2001237), a process that was also related to 12 out of the 58 illustrated genes. Nevertheless, among the genes involved in cell death, only Bcl2l11 was exclusively related to positive regulation of cell death. These miRNAs could be targeting Serpine1, Tgfbr1, Vegfa, Igf1, Hgf, Snai2, Rffl, Map2k5, Itgav, and Sgms1 mRNAs, which are related to inhibition of apoptotic externals signals.

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