PAX2 suppresses apoptosis in renal collecting duct cells.
PAX2 is a transcription factor belonging to the evolutionarily conserved paired box family and is required during development of the central nervous system and genitourinary axis. Mutations in the PAX2 gene cause a rare autosomal dominant renal-coloboma syndrome, characterized by optic nerve colobomas and renal hypoplasia. Recent analysis of a spontaneous PAX2 mutant mouse model (1Neu) revealed that the major cause of renal hypoplasia is reduced branching of the ureteric bud (UB) and fewer nephrons. We have observed that this abnormality is associated with a striking increase in the number of UB cells undergoing programmed cell death during nephrogenesis. To ascertain whether apoptosis is directly linked to the level of PAX2 expression, we have studied the role of PAX2 in cultured renal cells. We show that mIMCD-3 cells, a murine collecting duct cell line with high endogenous PAX2 expression, undergo apoptosis when transfected with anti-sense PAX2. In contrast, HEK293 cells expressing exogenous PAX2 are protected against apoptotic death induced by caspase-2. PAX2 has no effect on proliferation of embryonic kidney or in cultured kidney cells. Our observations imply a direct role for PAX2 in survival of ureteric bud cells.
Torban
E
E
Department of Pediatrics and Experimental Medicine, McGill University, Montreal, Quebec, Canada.
Eccles
M R
MR
Favor
J
J
Goodyer
P R
PR
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053143:Caspase 2; D061945:Caspase Inhibitors; D020169:Caspases / Q000494:pharmacology; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000502:physiology*; D004285:Dogs; D019085:Fluorescent Antibody Technique, Direct; D006720:Homozygote; D006801:Humans; D020287:In Situ Nick-End Labeling; D007685:Kidney Tubules, Collecting / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D051762:PAX2 Transcription Factor; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; C497319:Pax2 protein, mouse; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D053143:Caspase 2; D020169:Caspases