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 albuminuriaGrant 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 RD09/0076/0010
