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

Sara J. Holditch, Claire A. Schreiber, Peter C Harris, Nicholas F La Russo, Marina Ramirez-Alvarado, Alessandro Cataliotti, Vicente Torres, Yasuhiro H Ikeda

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
JournalKidney International
DOIs
StateAccepted/In press - Jul 22 2016

Fingerprint

Polycystic Kidney Diseases
Brain Natriuretic Peptide
Vasopressins
Disease Progression
Kidney
Calcium Signaling
Cystic Fibrosis
Antihypertensive Agents
Chronic Kidney Failure
Cysts
Homeostasis
Fibrosis
Epithelial Cells
Cell Proliferation
Hypertension
Calcium
Gene Expression
Weights and Measures
atrial natriuretic factor receptor A
Liver

Keywords

  • Adeno-associated virus
  • ADPKD
  • ARPKD
  • Congenital hepatic fibrosis
  • Gene therapy

ASJC Scopus subject areas

  • Medicine(all)
  • Nephrology

Cite this

B-type natriuretic peptide overexpression ameliorates hepatorenal fibrocystic disease in a rat model of polycystic kidney disease. / Holditch, Sara J.; Schreiber, Claire A.; Harris, Peter C; La Russo, Nicholas F; Ramirez-Alvarado, Marina; Cataliotti, Alessandro; Torres, Vicente; Ikeda, Yasuhiro H.

In: Kidney International, 22.07.2016.

Research output: Contribution to journalArticle

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