RAB-RABPHILIN SYSTEM IN INJURED HUMAN PODOCYTES STRESSED BY GLUCOSE OVERLOAD AND ANGIOTENSIN II.

Autores de INCLIVA

• Olga Martínez Arroyo

  Autor

• 

  Ana María Ortega Gutiérrez

  Autor

• Javier Perez Hernandez

  Autor

• 

  Felipe Javier Chaves Martínez

  Autor

• 

  Josep Redón Mas

  Autor

• 

  Raquel Cortés Vergaz

  Autor

Grupos y Plataformas de I+D+i

• Grupo de Estudio de Riesgo Cardiometabólico y Renal

  

  Established Researcher

  Raquel Cortés Vergaz

• Unidad de Genómica y Diabetes

  

  Established Researcher

  Felipe Javier Chaves Martínez

Abstract

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.

Licensed under Creative Commons Attribution CC-BY 4.0: © the American Physiological Society

Keywords

• angiotensin II; glucose; kidney injury; podocyte; Rab-Rabphilin system