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1.
Front Immunol ; 9: 640, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29670621

RESUMEN

Localized cutaneous leishmaniasis (LCL) is a chronic disease characterized by ulcerated skin lesion(s) and uncontrolled inflammation. The mechanisms underlying the pathogenesis of LCL are not completely understood, and little is known about posttranscriptional regulation during LCL. MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression and can be implicated in the pathogenesis of LCL. We investigated the involvement of miRNAs and their targets genes in human LCL using publicly available transcriptome data sets followed by ex vivo validation. Initial analysis highlighted that miRNA expression is altered during LCL, as patients clustered separately from controls. Joint analysis identified eight high confidence miRNAs that had altered expression (-1.5 ≤ fold change ≥ 1.5; p < 0.05) between cutaneous ulcers and uninfected skin. We found that the expression of miR-193b and miR-671 are greatly associated with their target genes, CD40 and TNFR, indicating the important role of these miRNAs in the expression of genes related to the inflammatory response observed in LCL. In addition, network analysis revealed that miR-193b, miR-671, and TREM1 correlate only in patients who show faster wound healing (up to 59 days) and not in patients who require longer cure times (more than 60 days). Given that these miRNAs are associated with control of inflammation and healing time, our findings reveal that they might influence the pathogenesis and prognosis of LCL.


Asunto(s)
Leishmania braziliensis/fisiología , Leishmaniasis Cutánea/genética , MicroARNs/genética , Receptor Activador Expresado en Células Mieloides 1/genética , Biomarcadores Farmacológicos , Antígenos CD40/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Leishmaniasis Cutánea/tratamiento farmacológico , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Fenómenos Fisiológicos de la Piel/genética , Resultado del Tratamiento , Cicatrización de Heridas/genética
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