The Rab-Rabphilin system in injured human podocytes stressed by glucose overload and angiotensin II
Kidney injury in hypertension and diabetes entails, among in other structures, damage in a key cell of the glomerular filtration barrier, the podocyte. Podocytes are polarized and highly differentiated cells in which vesicular transport, partly driven by Rab GTPases, is a relevant process. The prese...
| Autores: | , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Recursos: | INCLIVA |
| Repositorio: | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| OAI Identifier: | oai:incliva.fundanetsuite.com:p4563 |
| Acesso em linha: | https://incliva.portalinvestigacion.com/publicaciones/4563 |
| Access Level: | acceso abierto |
| Palavra-chave: | angiotensin II glucose kidney injury podocyte Rab-Rabphilin system |
| Resumo: | Kidney injury in hypertension and diabetes entails, among in other structures, damage in a key cell of the glomerular filtration barrier, the podocyte. Podocytes are polarized and highly differentiated cells in which vesicular transport, partly driven by Rab GTPases, is a relevant process. The present aim was to analyze Rab GTPases of the Rab-Rabphilin system in human immortalized podocytes and the impact of high glucose and angiotensin II. Furthermore, alterations of the system in urine cell pellets from hypertensive and diabetic patients were studied. Apoptosis was analyzed in podocytes and mRNA levels quantification, western blot and immunofluorescence were developed to quantify podocyte-specific molecules and Rab-Rabphilin components (Rab3A, Rab27A and Rabphilin3A). RTqPCR was performed on urinary cell pellet from patients. Results showed that differentiated cells had reduced protein levels of the Rab-Rabphillin system as compared with undifferentiated. After glucose overload and angiotensin II treatment, apoptosis was increased, and podocyte-specific proteins were reduced. Rab3A and Rab27A protein levels were increased under glucose overload and Rabphilin3A decreased. Furthermore, this system exhibited higher levels under stress conditions in a manner of angiotensin II dose and time treatment. Immunofluorescence imaging indicated different expression patterns of podocyte markers and Rab27A under treatments. Finally, Rab3A and Rab27A were increased in patient urine pellets and showed a direct relationship with albuminuria. Collectively, these results suggest that the Rab-Rabphilin system could be involved in the alterations observed in injured podocytes and that a mechanism may be activated to reduce damage through the vesicular transport enhancement directed by this system. |
|---|