Deletion of Pkd1 in renal stromal cells causes defects in the renal stromal compartment and progressive cystogenesis in the kidney.
Lab Invest
; 97(12): 1427-1438, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-28892094
ABSTRACT
Autosomal dominant polycystic kidney disease (ADPKD), caused by PKD1 and PKD2 gene mutations, is one of the most common genetic diseases, affecting up to 1 in 500 people. Mutations of PKD1 account for over 85% of ADPKD cases. However, mechanisms of disease progression and explanations for the wide range in disease phenotype remain to be elucidated. Moreover, functional roles of PKD1 in the renal stromal compartment are poorly understood. In this work, we tested if Pkd1 is essential for development and maintenance of the renal stromal compartment and if this role contributes to pathogenesis of polycystic kidney disease using a novel tissue-specific knockout mouse model. We demonstrate that deletion of Pkd1 from renal stromal cells using Foxd1-driven Cre causes a spectrum of defects in the stromal compartment, including excessive apoptosis/proliferation and extracellular matrix deficiency. Renal vasculature was also defective. Further, mutant mice showed epithelial changes and progressive cystogenesis in adulthood modeling human ADPKD. Altogether, we provide robust evidence to support indispensable roles for Pkd1 in development and maintenance of stromal cell derivatives by using a novel ADPKD model. Moreover, stromal compartment defects caused by Pkd1 deletion might serve as an important mechanism for pathogenesis of ADPKD.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Rim Policístico Autossômico Dominante
/
Canais de Cátion TRPP
/
Rim
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Lab Invest
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos