BASP1 promotes apoptosis in diabetic nephropathy.
Apoptosis contributes to the development of diabetic nephropathy (DN), but the mechanisms that lead to diabetes-induced cell death are not fully understood. Here, we combined a functional genomics screen for cDNAs that induce apoptosis in vitro with transcriptional profiling of renal biopsies from patients with DN. Twelve of the 138 full-length cDNAs that induced cell death in human embryonic kidney cells matched upregulated mRNA transcripts in tissue from human DN. Confirmatory screens identified induction of BASP1 in tubular cross sections of human DN tissue. In vitro, apoptosis-inducing conditions such as serum deprivation, high concentrations of glucose, and proinflammatory cytokines increased BASP1 mRNA and protein in human tubular epithelial cells. In normal cells, BASP1 localized to the cytoplasm, but in apoptotic cells, it colocalized with actin in the periphery. Overexpression of BASP1 induced cell death with features of apoptosis; conversely, small interfering RNA (siRNA)-mediated knockdown of BASP1 protected tubular cells from apoptosis. Supporting possible involvement of BASP1 in renal disease other than DN, we also observed significant upregulation of renal BASP1 in spontaneously hypertensive rats and a trend toward increased tubulointerstitial BASP1 mRNA in human hypertensive nephropathy. In summary, a combined functional genomics approach identified BASP1 as a proapoptotic factor in DN and possibly also in hypertensive nephropathy.
Sanchez-Niño
Maria Dolores
MD
Nefrología, Fundación Jiménez Díaz, Universidad Autonoma de Madrid and Instituto Reina Sofia de Investigaciones Nefrológicas-IRSIN, Madrid, Spain.
Sanz
Ana Belen
AB
Lorz
Corina
C
Gnirke
Andrea
A
Rastaldi
Maria Pia
MP
Nair
Viji
V
Egido
Jesus
J
Ruiz-Ortega
Marta
M
Kretzler
Matthias
M
Ortiz
Alberto
A
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000473:pathology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D051381:Rats; D012097:Repressor Proteins / Q000502:physiology*
C104089:BASP1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins