ArticleGene expression2017
Increased YAP Activation Is Associated With Hepatic Cyst Epithelial Cell Proliferation in ARPKD/CHF.
Article in Gene expression, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Defects of renal tubular homeostasis and cystogenesis in theiScience · 2024Article
- Dysregulation of the Scribble/YAP/β-catenin axis sustains the fibroinflammatory response in a PKHD1FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Inflammatory pathways and cholangiocarcinoma risk mechanisms and prevention.Advances in cancer research · 2022Review
- TAZ/Wnt-β-catenin/c-MYC axis regulates cystogenesis in polycystic kidney disease.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Epithelial Vasopressin Type-2 Receptors Regulate Myofibroblasts by a YAP-CCN2-Dependent Mechanism in Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2020Article
- Hippo signaling-a central player in cystic kidney disease?Pediatric nephrology (Berlin, Germany) · 2020Review
- The Hippo Pathway Is Essential for Maintenance of Apicobasal Polarity in the Growing Intestine ofGenetics · 2019Article
- Inhibition of Mast Cell Degranulation With Cromolyn Sodium Exhibits Organ-Specific Effects in Polycystic Kidney (PCK) Rats.International journal of toxicologyArticle
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Autosomal recessive polycystic kidney disease/congenital hepatic fibrosis (ARPKD/CHF) is a rare but fatal genetic disease characterized by progressive cyst development in the kidneys and liver. Liver cysts arise from aberrantly proliferative cholangiocytes accompanied by pericystic fibrosis and inflammation. Yes-associated protein (YAP), the downstream effector of the Hippo signaling pathway, is implicated in human hepatic malignancies such as hepatocellular carcinoma, cholangiocarcinoma, and hepatoblastoma, but its role in hepatic cystogenesis in ARPKD/CHF is unknown. We studied the role of the YAP in hepatic cyst development using polycystic kidney (PCK) rats, an orthologous model of ARPKD, and in human ARPKD/CHF patients. The liver cyst wall epithelial cells (CWECs) in PCK rats were highly proliferative and exhibited expression of YAP. There was increased expression of YAP target genes, Ccnd1 (cyclin D1) and Ctgf (connective tissue growth factor), in PCK rat livers. Extensive expression of YAP and its target genes was also detected in human ARPKD/CHF liver samples. Finally, pharmacological inhibition of YAP activity with verteporfin and short hairpin (sh) RNA-mediated knockdown of YAP expression in isolated liver CWECs significantly reduced their proliferation. These data indicate that increased YAP activity, possibly through dysregulation of the Hippo signaling pathway, is associated with hepatic cyst growth in ARPKD/CHF.
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