Premium
Natriuretic Peptides Exert Marked Renoprotective Effects Via Activation of the Natriuretic Peptide Receptor GC‐A in Podocytes
Author(s) -
Staffel Janina,
Valletta Daniela,
Federlein Anna,
Kuhn Michaela,
Schweda Frank
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.808.6
Subject(s) - endocrinology , medicine , podocyte , atrial natriuretic peptide , albuminuria , chemistry , mineralocorticoid receptor , renal function , receptor , kidney , proteinuria
According to the vascular and tubular effects of the natriuretic peptides ANP and BNP, their common receptor guanylyl cyclase A (GC‐A) is expressed in renal vessels and tubular cells. Additionally GC‐A is expressed in podocytes, with unknown functions. In order to clarify the role of GC‐A in podocytes we generated mice with podocyte specific deletion of GC‐A (Podo/GC‐A KO). Podocytes of control mice (Podo/GC‐A CTR) had higher GC‐A mRNA expression than all other glomerular and tubular cells. GC‐A mRNA in podocytes of Podo/GC‐A KO was reduced to 1% of CTR. Despite of this effective deletion, Podo/GC‐A KO and CTR did not differ regarding their blood pressure, glomerular filtration rate, albuminuria, salt and water excretion under control conditions. Moreover, infusion of ANP and BNP resulted in similar increases in the GFR and in the renal perfusion in KO and CTR. Since natriuretic peptides are renoprotective in several disease models, we next investigated whether these protective properties are related to GC‐A activation in podocytes. Application of the mineralocorticoid DOCA + a high salt intake for 5 weeks induced similar slight increases in the blood pressure in KO and CTR. However, compared with CTR, Podo/GC‐A KO developed massive albuminuria (CTR: 15‐fold vs. control, KO: 300‐fold vs. control), a reduction of GFR and marked glomerular damage including podocyte foot process effacement, mesangial expansion and glomerulosclerosis. In conclusion, ANP/GC‐A/cGMP signaling in podocytes does not appear to be involved in the acute regulation of kidney function. However it has marked protective effects on podocyte integrity attenuating massive albuminuria and renal failure in response to kidney damage.