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dc.contributor.authorSanchez-Niño, M D
dc.contributor.authorFernandez-Fernandez, B
dc.contributor.authorPerez-Gomez, M V
dc.contributor.authorPoveda, J
dc.contributor.authorSanz, A B
dc.contributor.authorCannata-Ortiz, P
dc.contributor.authorRuiz-Ortega, M
dc.contributor.authorEgido, J
dc.contributor.authorSelgas, R
dc.contributor.authorOrtiz, A
dc.identifier.citationCell Death Dis.2015 Feb;(6):e1644
dc.description.abstractAlbuminuria 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.
dc.subject.meshBlotting, Western
dc.subject.meshCalmodulin-Binding Proteins
dc.subject.meshCell Line
dc.subject.meshCytoskeletal Proteins
dc.subject.meshKidney Tubules, Proximal
dc.subject.meshMembrane Proteins
dc.subject.meshMicroscopy, Confocal
dc.subject.meshNerve Tissue Proteins
dc.subject.meshRNA, Small Interfering
dc.subject.meshRepressor Proteins
dc.titleAlbumin-induced apoptosis of tubular cells is modulated by BASP1.
dc.identifier.journalCell death & disease
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. La Paz > Artículos

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