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La absorción de antimiR por las células epiteliales del túbulo proximal humano se produce predominantemente por

Emily K Glover¹, Rolando Berlinguer-Palmini², Emily R Thompson³

¹Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK. emily.glover@newcastle.ac.uk.

Scientific reports

|August 28, 2025

Resumen

Los inhibidores de microARN (antimiR) pueden administrarse a las células renales humanas in vitro sin agentes de transfección. La macropinocitosis es la vía principal para la captación de antimiR por las células epiteliales del túbulo proximal.

Área de la Ciencia:

Ciencias Biomédicas
Biología molecular
Medicina del riñón

Sus antecedentes:

Los inhibidores de microARN (antimiR) muestran potencial terapéutico para enfermedades renales, como la lesión por isquemia-reperfusión.
La administración eficiente de antimiRs a las células renales objetivo sigue siendo un desafío.
Estudios previos sugieren la absorción endocítica de antimiR en modelos de perfusión renal ex situ.

Objetivo del estudio:

Investigar in vitro la absorción de antimiR por las células epiteliales primarias del túbulo proximal humano (PTEC).
Identificar el mecanismo endocítrico específico responsable de la entrada de antimiR en el PTEC.
Determinar si se requieren reactivos de transfección para la administración de antimiR al PTEC in vitro.

Principales métodos:

Se aislaron PTEC humanos primarios de riñones de donantes y se cultivaron.
La absorción de antimiR se evaluó mediante microscopía de fluorescencia y cuantificación de las señales fluorescentes.
La endocitosis se confirmó utilizando marcadores endocíticos y ensayos de absorción dependientes de la temperatura.
Se investigaron vías endocíticas específicas utilizando inhibidores de la endocitosis mediada por los receptores (megalina) y la macropinocitosis.

Principales resultados:

El PTEC demostró una absorción significativa de los antimiR marcados con fluorescencia in vitro.
La absorción exhibió un patrón vesicular, consistente con la endocitosis.
La absorción de antimiR fue dependiente de la temperatura y co-localizada con marcadores endocíticos.
La inhibición de la macropinocitosis redujo significativamente la absorción de antimiR, mientras que la inhibición de la megalina no tuvo ningún efecto.

Conclusiones:

Los antimiR se pueden administrar eficazmente en el PTEC humano primario in vitro sin necesidad de reactivos de transfección.
La macropinocitosis es la vía endocítica predominante para la entrada de antimiR en el PTEC.
Estos hallazgos apoyan el potencial de estrategias de administración de antimiR no virales en el tratamiento de enfermedades renales.

Palabras clave:

El antimiR La endocitosis La macropinocitosis Células epiteliales del túbulo proximal Tráfico de personas antimiR

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