B-type natriuretic peptide overexpression ameliorates hepatorenal fibrocystic disease in a rat model of polycystic kidney disease
| Autor: | Alessandro Cataliotti, Claire A. Schreiber, Nicholas F. LaRusso, Sara J. Holditch, Vicente E. Torres, Yasuhiro Ikeda, Peter C. Harris, Marina Ramirez-Alvarado |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Vasopressin Vasopressins medicine.drug_class Genetic enhancement Genetic Vectors Biology Kidney Cyclase Article Rats Sprague-Dawley Pathogenesis 03 medical and health sciences Parvovirinae Fibrosis Internal medicine Natriuretic Peptide Brain Cyclic AMP medicine Polycystic kidney disease Natriuretic peptide Animals Humans Cyclic GMP Cell Proliferation Polycystic Kidney Autosomal Recessive Cysts Liver Diseases Epithelial Cells medicine.disease Rats Disease Models Animal 030104 developmental biology Endocrinology Liver Nephrology Hypertension Disease Progression cardiovascular system Congenital hepatic fibrosis Female Receptors Atrial Natriuretic Factor Signal Transduction |
| Zdroj: | Kidney International. 92:657-668 |
| ISSN: | 0085-2538 |
| DOI: | 10.1016/j.kint.2017.02.017 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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