Pax2 expression occurs in renal medullary epithelial cells in vivo and in cell culture, is osmoregulated, and promotes osmotic tolerance.
Pax2 is a transcription factor that is crucial for kidney development, and it is also expressed in the normal adult kidney, where its physiological function is unknown. In the present study, we find by cDNA microarray analysis that Pax2 expression in second-passage mouse inner-medullary epithelial cells is increased by a high NaCl concentration, which is significant because NaCl levels are normally high in the inner medulla in vivo, and varies with urinary concentration. Furthermore, a high NaCl concentration increases Pax2 mRNA and protein expression in mouse inner medullary collecting duct (mIMCD3) cells, and its transcriptional activity. Pax2 mRNA and protein expression is high in normal adult mouse renal inner medulla but much lower in renal cortex. Pax2 protein is present in collecting duct cells in both renal medulla and cortex and in thin descending limbs of Henle's loop in inner medulla. Treating Brattleboro rats with desamino-Cys-1,d-Arg-8 vasopressin, which increases inner-medullary NaCl concentration, causes a 4-fold increase in inner-medullary Pax2 protein. Treatment with furosemide, which decreases inner-medullary NaCl, reduces inner-medullary Pax2 mRNA and protein. Pax2-specific short interfering RNA increases high NaCl concentration-induced activation of caspase-3 and apoptotic bodies in mIMCD3 cells. We thus conclude that (i) Pax2 is expressed in normal renal medulla, (ii) its expression is regulated there by the normally high and variable NaCl concentration, and (iii) it protects renal medullary cells from high NaCl concentration-induced apoptosis.
Cai
Qi
Q
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-1603, USA.
Dmitrieva
Natalia I
NI
Ferraris
Joan D
JD
Brooks
Heddwen L
HL
van Balkom
Bas W M
BW
Burg
Maurice
M
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D007679:Kidney Medulla / Q000378:metabolism*; D008297:Male; D051379:Mice; D051762:PAX2 Transcription Factor; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011910:Rats, Brattleboro; D012965:Sodium Chloride / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D014508:Urea / Q000494:pharmacology; D014882:Water-Electrolyte Balance
D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D012965:Sodium Chloride; D014508:Urea; D003894:Deamino Arginine Vasopressin