Albumin-induced apoptosis of tubular cells is modulated by BASP1
Entity
UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ); Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)Publisher
Nature Publishing GroupDate
2015-01-01Citation
10.1038/cddis.2015.1
Cell Death and Disease 6.2 (2015): e1644
ISSN
2041-4889DOI
10.1038/cddis.2015.1Funded by
Grant support: FIS PS09/00447, PI13/00047, CP14/ 00133, ISCIII-RETIC, REDinREN/RD06/0016/and RD012/0021 FEDER funds, Comunidad de Madrid/CIFRA S2010/BMD-2378. Salary support: FIS to MDSN and ABS (Miguel Servet), Beatriz Fernandez-Fernandez (Rio Hortega). Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to AO. IIS-FJD Biobank RD09/0076/00101Project
Gobierno de España. PS09/00447; Comunidad de Madrid. S2010/BMD-2378/CIFRAEditor's Version
http://dx.doi.org/10.1038/cddis.2015.1Subjects
Albuminaria; Epithelial cells; Tubular cells; MedicinaRights
© 2015 Macmillan Publishers LimitedAbstract
Albuminuria promotes tubular injury and cell death, and is associated with faster progression of chronic kidney disease (CKD) to
end-stage renal disease. However, the molecular mechanisms regulating tubular cell death in response to albuminuria are not fully
understood. Brain abundant signal protein 1 (BASP1) was recently shown to mediate glucose-induced apoptosis in tubular cells.
We have studied the role of BASP1 in albumin-induced tubular cell death. BASP1 expression was studied in experimental
puromycin aminonucleoside-induced nephrotic syndrome in rats and in human nephrotic syndrome. The role of BASP1 in
albumin-induced apoptosis was studied in cultured human HK2 proximal tubular epithelial cells. Puromycin aminonucleoside
induced proteinuria and increased total kidney BASP1 mRNA and protein expression. Immunohistochemistry localized the
increased BASP1 to tubular cells. BASP1 expression colocalized with deoxynucleotidyl-transferase-mediated dUTP nick-end
labeling staining for apoptotic cells. Increased tubular BASP1 expression was observed in human proteinuric nephropathy by
immunohistochemistry, providing evidence for potential clinical relevance. In cultured tubular cells, albumin induced apoptosis
and increased BASP1 mRNA and protein expression at 6–48 h. Confocal microscopy localized the increased BASP1 expression
in albumin-treated cells mainly to the perinuclear area. A peripheral location near the cell membrane was more conspicuous in
albumin-treated apoptotic cells, where it colocalized with actin. Inhibition of BASP1 expression by a BASP1 siRNA protected from
albumin-induced apoptosis. In conclusion, albumin-induced apoptosis in tubular cells is BASP1-dependent. This information may
be used to design novel therapeutic approaches to slow CKD progression based on protection of tubular cells from the adverse
consequences of albuminuria
Files in this item
Google Scholar:Sánchez Niño, María Dolores
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Fernandez, B.
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Perez-Gomez, M. V.
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Poveda de Agustín, Jesús
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Sanz, A. B.
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Cannata, Pablo
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Ruiz Ortega, Marta
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Egido, J.
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Selgas, R.
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Ortiz Arduán, Alberto
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