Decreased renal corin expression contributes to sodium retention in proteinuric kidney diseases.
Patients with proteinuric kidney diseases often have symptoms of salt and water retention. It has been hypothesized that dysregulated sodium absorption is due to increased proteolytic cleavage of epithelial sodium channels (ENaCs) and increased Na,K-ATPase expression. Microarray analysis identified a reduction in kidney corin mRNA expression in rat models of puromycin aminonucleoside-induced nephrotic syndrome and acute anti-Thy1 glomerulonephritis (GN). As atrial natriuretic peptide (ANP) resistance is a mechanism accounting for volume retention, we analyzed the renal expression and function of corin; a type II transmembrane serine protease that converts pro-ANP to active ANP. Immunohistochemical analysis found that corin colocalized with ANP. The nephrotic and glomerulonephritic models exhibited concomitant increased pro-ANP and decreased ANP protein levels in the kidney consistent with low amounts of corin. Importantly, kidneys from corin knockout mice had increased amounts of renal β-ENaC and its activators, phosphodiesterase (PDE) 5 and protein kinase G II, when compared to wild-type mice. A similar expression profile was also found in cell culture suggesting the increase in PDE5 and kinase G II could account for the increase in β-ENaC seen in nephrotic syndrome and GN. Thus, we suggest that corin might be involved in the salt retention seen in glomerular diseases.
Polzin
Danny
D
Institute of Anatomy, Charité Universitätsmedizin, Berlin, Germany.
Kaminski
Henriette J
HJ
Kastner
Christian
C
Wang
Wei
W
Krämer
Stephanie
S
Gambaryan
Stepan
S
Russwurm
Michael
M
Peters
Harm
H
Wu
Qingyu
Q
Vandewalle
Alain
A
Bachmann
Sebastian
S
Theilig
Franziska
F
D000818:Animals; D051399:Aquaporin 2 / Q000032:analysis; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis; D000242:Cyclic AMP / Q000096:biosynthesis; D053503:Epithelial Sodium Channels / Q000032:analysis; D005921:Glomerulonephritis / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D009404:Nephrotic Syndrome / Q000378:metabolism; D011507:Proteinuria / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*
D051399:Aquaporin 2; D053503:Epithelial Sodium Channels; D009320:Atrial Natriuretic Factor; D012964:Sodium; D000242:Cyclic AMP; C119812:CORIN protein, human; C485617:Corin protein, mouse; D012697:Serine Endopeptidases; C492879:corin protein, rat