B-type natriuretic peptide overexpression ameliorates hepatorenal fibrocystic disease in a rat model of polycystic kidney disease

Abstract

Polycystic kidney disease (PKD) involves progressive hepatorenal cyst expansion and fibrosis, frequently leading to end-stage renal disease. Increased vasopressin and cAMP signaling, dysregulated calcium homeostasis, and hypertension play major roles in PKD progression. The guanylyl cyclase A agonist, B-type natriuretic peptide (BNP), stimulates cGMP and shows anti-fibrotic, anti-hypertensive, and vasopressin-suppressive effects, potentially counteracting PKD pathogenesis. Here, we assessed the impacts of guanylyl cyclase A activation on PKD progression in a rat model of PKD. Sustained BNP production significantly reduced kidney weight, renal cystic indexes and fibrosis, in concert with suppressed hepatic cystogenesis in vivo. In vitro, BNP decreased cystic epithelial cell proliferation, suppressed fibrotic gene expression, and increased intracellular calcium. Together, our data demonstrate multifaceted effects of sustained activation of guanylyl cyclase A on polycystic kidney and liver disease. Thus, targeting the guanylyl cyclase A-cGMP axis may provide a novel therapeutic strategy for hepatorenal fibrocystic diseases.

Renal Corin Is Essential for Normal Blood Pressure and Sodium Homeostasis

“…Conversely, reduced renal corin expression has been reported in rat kidney disease models [ 36 , 72 ] and in patients with chronic kidney disease and sodium retention [ 41 ]. In previous studies in animal models and patients, altered natriuretic peptide expression and processing have been found as mechanisms underlying hypertension and cardiorenal disease [ 73 , 74 , 75 , 76 , 77 ]. In a recent study, altered corin expression in the heart was also found in patients with chronic kidney disease [ 78 ].…”