MicroRNA-21 e microRNA-148a regulam PTEN, NO e ROS na leishmaniose canina
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Data
2023-01-18
Autores
Freitas, Jéssica Henrique de
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Universidade Estadual Paulista (Unesp)
Resumo
A leishmaniose visceral canina (CanL) representa uma grave ameaça à saúde pública em vários países. A progressão da doença depende do grau de supressão da resposta imune. Os microRNAs (miRs) modulam a tradução do mRNA em proteínas e regulam várias funções celulares e vias associadas às respostas imunes. MiR-21 e miR-148a podem alterar a carga parasitária e os macrófagos M1 são as principais células na atividade leishmanicida de cães. Um estudo anterior encontrou aumento de miR-21 e miR-148a em leucócitos esplênicos (LE) de cães com CanL usando a análise de microarranjo, e a análise in silico identificou alvos da via PTEN. PTEN está envolvido na regulação imune de macrófagos. Medimos PTEN e a produção de espécies reativas de oxigênio (ROS) e óxido nítrico (NO) após transfecção com mimic e inhibitor de miR-21 e miR-148a em LE de cães com CanL. Os níveis de PTEN aumentaram, NO e ROS diminuíram em LEs de cães com CanL. A inibição do miRNA-21 resultou em aumentos de PTEN; em contraste, o PTEN diminuiu após a inibição do miR-148a. Os níveis de nitrito aumentaram após a transfecção com o inibidor de miR-21, mas diminuíram com o inibidor de miR-148a. O aumento de miR-21 promoveu redução nos níveis de ROS e NO. Esses achados sugerem que miR-21 e miR-148a modulam a resposta imune em cães com CanL por meio de PTEN, NO e ROS.
Canine Visceral leishmaniasis (CanL) poses a severe public health threat in several countries. Disease progression depends on the degree of immune response suppression. MicroRNAs (miRs) modulate mRNA translation into proteins and regulate various cellular functions and pathways associated with immune responses. MiR-21 and miR-148a can alter the parasite load and M1 macrophages are the principal cells in dog's leishmanicidal activity. A previous study found increased miR-21 and miR-148a in splenic leukocytes (SL) of dogs with CanL using microarray analysis and in silico analysis, identified PTEN pathway targets. PTEN is involved in the immune regulation of macrophages. We measured PTEN and the production of reactive oxygen species (ROS) and nitric oxide (NO) after transfection SL of dogs with CanL with mimic and inhibition of miR-21 and miR-148a. PTEN levels increased, NO and ROS decreased in SLs from dogs with CanL. Inhibition of miRNA-21 resulted in PTEN increases; in contrast, PTEN decreased after miR-148a inhibition. Nitrite levels increased after transfection with miR-21 inhibitor but were decreased with miR-148a inhibitor. The increase in miR-21 promoted a reduction in ROS and NO levels. These findings suggest that miR-21 and miR-148a modulate the immune response in dogs with CanL through PTEN, NO, and ROS.
Canine Visceral leishmaniasis (CanL) poses a severe public health threat in several countries. Disease progression depends on the degree of immune response suppression. MicroRNAs (miRs) modulate mRNA translation into proteins and regulate various cellular functions and pathways associated with immune responses. MiR-21 and miR-148a can alter the parasite load and M1 macrophages are the principal cells in dog's leishmanicidal activity. A previous study found increased miR-21 and miR-148a in splenic leukocytes (SL) of dogs with CanL using microarray analysis and in silico analysis, identified PTEN pathway targets. PTEN is involved in the immune regulation of macrophages. We measured PTEN and the production of reactive oxygen species (ROS) and nitric oxide (NO) after transfection SL of dogs with CanL with mimic and inhibition of miR-21 and miR-148a. PTEN levels increased, NO and ROS decreased in SLs from dogs with CanL. Inhibition of miRNA-21 resulted in PTEN increases; in contrast, PTEN decreased after miR-148a inhibition. Nitrite levels increased after transfection with miR-21 inhibitor but were decreased with miR-148a inhibitor. The increase in miR-21 promoted a reduction in ROS and NO levels. These findings suggest that miR-21 and miR-148a modulate the immune response in dogs with CanL through PTEN, NO, and ROS.
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microRNA, ROS, NO, PTEN, Nitrito, Leishmania infantum, Leucócitos esplênicos, Nitrite, Splenic leukocytes