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VRAC coordina el equilibrio entre la absorción de nutrientes y la defensa antimicrobiana en enterocitos contra la

Xin Yi¹, Shiqing Zhang^2,3, Xinpei Gu¹

¹Guangdong Provincial Key Laboratory of New Drug Screening and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.

Nature communications

|February 24, 2026

Resumen

El canal aniónico regulado por volumen (VRAC) es crucial para la salud intestinal. Su deficiencia en enterocitos altera la absorción de nutrientes y la defensa, empeorando la enfermedad inflamatoria intestinal y el cáncer colorrectal.

Área de la Ciencia:

Gastroenterología; Biología Molecular; Inmunología

Sus antecedentes:

Los enterocitos realizan la absorción de nutrientes y la secreción de péptidos antimicrobianos (AMP).; Los canales aniónicos regulados por volumen (VRAC) son canales iónicos osmosensibles.; Se desconoce el papel de VRAC en los enterocitos y la enfermedad inflamatoria intestinal (EII).

Objetivo del estudio:

Investigar el papel de VRAC, específicamente la subunidad LRRC8A, en los enterocitos.; Determinar el impacto de la deficiencia de VRAC en la homeostasis intestinal, la inflamación y el cáncer colorrectal.; Explorar el potencial terapéutico del ácido retinoico y Lactobacillus en condiciones de deficiencia de VRAC.

Principales métodos:

Se generaron ratones con silenciamiento específico de LRRC8A en el epitelio intestinal (IEC).; Se analizó la maduración, zonación y producción de AMP de los enterocitos.; Se evaluó el metabolismo del ácido retinoico y la composición de la microbiota intestinal.; Se administraron especies de ácido retinoico y Lactobacillus a ratones deficientes en VRAC.

Principales resultados:

El silenciamiento específico de LRRC8A en el epitelio intestinal (IEC) exacerbó la colitis y el cáncer colorrectal asociado a la inflamación.; La deficiencia de VRAC alteró la maduración y la zonación de los enterocitos, modificando la producción de AMP y la absorción de nutrientes.; Se alteró el metabolismo del ácido retinoico y se observó disbiosis de la microbiota intestinal.; La suplementación con ácido retinoico y la administración de Lactobacillus aliviaron la inflamación.

Conclusiones:

VRAC es esencial para mantener la función de los enterocitos y la homeostasis intestinal.; La deficiencia de VRAC altera el equilibrio entre la absorción de nutrientes y la defensa antimicrobiana, contribuyendo a la EII y al cáncer colorrectal.; La modulación de las vías mediadas por VRAC, incluido el metabolismo del ácido retinoico y la microbiota intestinal, ofrece estrategias terapéuticas potenciales para las enfermedades intestinales.

Palabras clave:

enterocitos enfermedad inflamatoria intestinal cáncer colorrectal microbiota intestinal ácido retinoico

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