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

Autor: Maria José Panadés, Elvira Fernández, Maite Caus, Neus Pedraza, Milica Bozic, Eloi Garí, Marta Ruiz-Ortega, Ana Martínez, Pilar Gallel, Raúl R. Rodrigues-Diez, Jose M. Valdivielso
Přispěvatelé: UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
General Physics and Astronomy
Gene Expression
Vimentin
Kidney
urologic and male genital diseases
p38 Mitogen-Activated Protein Kinases
Pathogenesis
Mice
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Fibrosis
lcsh:Science
Pathogenesis of renal TIF
Cytoskeleton
Mice
Knockout
Mitogen-Activated Protein Kinase 1
Multidisciplinary
Mitogen-Activated Protein Kinase 3
Ronyons -- Fibrosi
Disruption of SNCA
Phenotype
Gene Knockdown Techniques
alpha-Synuclein
Kidney Diseases
Signal Transduction
Ureteral Obstruction
Medicina
Renal epithelial cells
Science
Biology
General Biochemistry
Genetics and Molecular Biology
Article
Cell Line
Transforming Growth Factor beta1
03 medical and health sciences
Kidney fibrosis
Downregulation and upregulation
medicine
Gene silencing
Animals
Humans
Protein Kinase Inhibitors
urogenital system
Kidney metabolism
Epithelial Cells
General Chemistry
medicine.disease
Neuronal protein
Actins
Mice
Inbred C57BL
030104 developmental biology
Cancer research
biology.protein
Tubulointerstitial fibrosis
lcsh:Q
SNCA
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Kidney disease
Zdroj: Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020)
Recercat: Dipósit de la Recerca de Catalunya
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Nature Communications
Biblos-e Archivo: Repositorio Institucional de la UAM
Universidad Autónoma de Madrid
Repositorio Abierto de la UdL
Universitad de Lleida
Biblos-e Archivo. Repositorio Institucional de la UAM
instname
Recercat. Dipósit de la Recerca de Catalunya
ISSN: 2041-1723
Popis: 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.
This work was supported by research grants PI15/00960 and PI17/00119 from the Instituto de Salud Carlos III (ISCII, Spanish Ministry of Economy and Competitiveness) and REDinREN (RD12/0021). The work on human kidney tissue samples was supported by the IRBLleida Biobank (B.0000682) and PLATAFORMA BIOBANCOS PT17/0015/ 0027. M.B. was supported by the REDinREN (RD12/0021/0026) and Department of Health, Government of Catalonia (PERIS 2016-2020, SLT002/16/00178). M.C. was supported by the studentship from the Catalan Government (AGAUR). R.R.R-D. was supported by a grant from the Comunidad Autonóma de Madrid (B2017/BMD-3751 NOVELREN-CM).
Databáze: OpenAIRE
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