Evidence for a “Pathogenic Triumvirate” in Congenital Hepatic Fibrosis in Autosomal Recessive Polycystic Kidney Disease
Year: 2016
Type: article
Abstract: gene. Congenital hepatic fibrosis (CHF) associated with ARPKD is characterized by the presence of hepatic cysts derived from dilated bile ducts and a robust, pericystic fibrosis. Cyst growth, due to cyst wall epithelial cell hyperproliferation and fluid secretion, is thought to be the driving force behind disease progression. Liver fibrosis is a wound healing response in which collagen accumulates in the liver due to an imbalance between extracellular matrix synthesis and degradation. Whereas both hyperproliferation and pericystic fibrosis are hallmarks of CHF/ARPKD, whether or not these two processes influence one another remains unclear. Additionally, recent studies demonstrate that inflammation is a common feature of CHF/ARPKD. Therefore, we propose a "pathogenic triumvirate" consisting of hyperproliferation of cyst wall growth, pericystic fibrosis, and inflammation which drives CHF/ARPKD progression. This review will summarize what is known regarding the mechanisms of cyst growth, fibrosis, and inflammation in CHF/ARPKD. Further, we will discuss the potential advantage of identifying a core pathogenic feature in CHF/ARPKD to aid in the development of novel therapeutic approaches. If a core pathogenic feature does not exist, then developing multimodality therapeutic approaches to target each member of the "pathogenic triumvirate" individually may be a better strategy to manage this debilitating disease.
Source: BioMed Research International
DOI: 10.1155/2016/4918798
Institution: University of Kansas Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,680
Funders: University of Alabama at Birmingham, University of Alabama, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1041550091, G13016703, G1377672508, G1958400685, G2738298465, G2850908965, G362742471, G4824971037, G5560837329, G602775177, Mechanisms of Liver Regeneration After Acetaminophen-Induced Acute Liver Failure, G6847597861, G7050944511, G7658266417, G781754001, G8239578312, G837244489, G865751187, G8700317804, G9000004278, G9000023610, G9000043943, G9000099149, G9000145605, G9000201249, G9000281922, G9000333407, Kansas IDeA Network of Biomedical Research Excellence 5
OpenAlex ID: W2551251981