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Publicaciones > Miguel et al
The pHLIP system as a vehicle for microRNAs in the kidney.
1. Programa de Procesos Fisiológicos y Patológicos, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, España. Electronic address:. 2. Programa de Procesos Fisiológicos y Patológicos, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, España. 3. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química Andrés M. del Río (IQAR), Universidad de Alcalá, IRYCIS, Alcalá de Henares, Madrid, España. 4. Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, Estados Unidos. 5. Department of Medicine and Medical Specialties, Research Foundation of the University Hospital Príncipe de Asturias, IRYCIS, Alcalá University, Alcalá de Henares, Madrid, España.
a. vmiguel@cbm.csic.es
Palabras clave: Fibrosis renal; PNA; PNAs; Renal fibrosis; miRNA; miRNAs; pHLIP
Resumen
MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene expression through post-transcriptional repression of their target messenger RNAs. A study of changes in expression of certain miRNAs in the kidney has supplied evidence on their pathogenic role and therapeutic potential in nephrology. This review proposes a nanotechnology approach based on the binding of analogs or inhibitors of miRNAs formed by peptide nucleic acids (PNAs) to peptides with a transmembrane structure sensitive to a low pH, called pHLIPs (pH [low] insertion peptides). The review draws on the concept that an acidic pH in the microenvironment of the renal tubule may facilitate concentration and distribution of the pHLIP-PNA complex in this organ. In this context, we have demonstrated for the first time that targeted administration of miR-33 inhibitors with the pHLIP system effectively prevents the development of renal fibrosis, thus opening up this technology to new strategies for diagnosis and treatment of kidney diseases.