Apoptotic cell death in renal injury: the rationale for intervention.
Cell number abnormalities are frequent in renal diseases, and range from the hypercellularity of postinfectious glomerulonephritis to the cell depletion of chronic renal atrophy. Recent research has shown that apoptosis and its regulatory mechanisms contribute to cell number regulation in the kidney. The potential role of apoptosis ranges from induction and progression to repair of renal injury. Death ligands and receptors, such as tumor necrosis factor and Fas ligand, proapoptotic and antiapoptotic Bcl2 family members and caspases have all been shown to participate in apoptosis regulation in the course of renal cell injury. However, the precise role of these proteins is unclear, and the participation of most known apoptosis regulatory proteins has not been studied. We now review the role of apoptosis in renal injury, the potential molecular targets of therapeutic intervention, the therapeutic weapons to modulate the activity of these targets and the few examples of therapeutic intervention on apoptosis, with emphasis on the acute tubular necrosis.
Ortiz
A
A
Division of Nephrology, Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Fundacion Renal Iñigo Alvarez de Todelo, Madrid, Spain. aortiz@fjd.es
Justo
P
P
Catalán
M P
MP
Sanz
A B
AB
Lorz
C
C
Egido
J
J
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D007683:Kidney Tubular Necrosis, Acute / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D020169:Caspases