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Protective role of renal proximal tubular alpha-synuclein in the pathogenesis of kidney fibrosis

Author

Listed:
  • Milica Bozic

    (Vascular and Renal Translational Research Group, Institute for Biomedical Research in Lleida (IRBLleida) and RedInRen Retic)

  • Maite Caus

    (Vascular and Renal Translational Research Group, Institute for Biomedical Research in Lleida (IRBLleida) and RedInRen Retic)

  • Raul R. Rodrigues-Diez

    (Cellular and Molecular Biology in Renal and Vascular Pathology, IIS-Fundación Jiménez Díaz-Universidad Autónoma Madrid)

  • Neus Pedraza

    (University of Lleida)

  • Marta Ruiz-Ortega

    (Cellular and Molecular Biology in Renal and Vascular Pathology, IIS-Fundación Jiménez Díaz-Universidad Autónoma Madrid)

  • Eloi Garí

    (University of Lleida)

  • Pilar Gallel

    (University Hospital Arnau de Vilanova and University of Lleida)

  • Maria José Panadés

    (University Hospital Arnau de Vilanova and University of Lleida)

  • Ana Martinez

    (Vascular and Renal Translational Research Group, Institute for Biomedical Research in Lleida (IRBLleida) and RedInRen Retic)

  • Elvira Fernández

    (Vascular and Renal Translational Research Group, Institute for Biomedical Research in Lleida (IRBLleida) and RedInRen Retic)

  • José Manuel Valdivielso

    (Vascular and Renal Translational Research Group, Institute for Biomedical Research in Lleida (IRBLleida) and RedInRen Retic)

Abstract

Kidney fibrosis is a highly deleterious process and a final manifestation of chronic kidney disease. Alpha-(α)-synuclein (SNCA) is an actin-binding neuronal protein with various functions within the brain; however, its role in other tissues is unknown. Here, we describe the expression of SNCA in renal epithelial cells and demonstrate its decrease in renal tubules of murine and human fibrotic kidneys, as well as its downregulation in renal proximal tubular epithelial cells (RPTECs) after TGF-β1 treatment. shRNA-mediated knockdown of SNCA in RPTECs results in de novo expression of vimentin and α-SMA, while SNCA overexpression represses TGF-β1-induced mesenchymal markers. Conditional gene silencing of SNCA in RPTECs leads to an exacerbated tubulointerstitial fibrosis (TIF) in two unrelated in vivo fibrotic models, which is associated with an increased activation of MAPK-p38 and PI3K-Akt pathways. Our study provides an evidence that disruption of SNCA signaling in RPTECs contributes to the pathogenesis of renal TIF by facilitating partial epithelial-to-mesenchymal transition and extracellular matrix accumulation.

Suggested Citation

  • Milica Bozic & Maite Caus & Raul R. Rodrigues-Diez & Neus Pedraza & Marta Ruiz-Ortega & Eloi Garí & Pilar Gallel & Maria José Panadés & Ana Martinez & Elvira Fernández & José Manuel Valdivielso, 2020. "Protective role of renal proximal tubular alpha-synuclein in the pathogenesis of kidney fibrosis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15732-9
    DOI: 10.1038/s41467-020-15732-9
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