Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease

• DOI: 10.1038/s41598-018-21132-3
• Publication Date: 2018-02-14T11:29:02Z
• Authors: Jessica Idowu; Trisha Home; Nisha Patel; Brenda Magenheimer; Pamela V. Tran; Robin L. Maser; Christopher J. Ward; James P. Calvet; Darren P. Wallace; Madhulika Sharma
• Keywords: PKD1

Polycystic kidney disease (PKD) is a genetic disorder characterized by fluid-filled cysts in the and liver that ultimately leads to end-stage renal disease. Currently there no globally approved therapy for PKD. The Notch signaling pathway regulates cellular processes such as proliferation de-differentiation, which are hallmarks of Thus we hypothesized plays critical role Evaluation protein expression components kidneys Autosomal Recessive PKD (ARPKD) Dominant (ADPKD) mouse models ADPKD patients revealed members, particularly Notch3, were consistently upregulated or activated cyst-lining epithelial cells. Notch3 correlated with rapidly growing co-localized marker, PCNA. Importantly, inhibition significantly decreased forskolin-induced activation primary human cells, reduced cyst formation growth cells cultured collagen gels. our data indicate aberrantly facilitates cell PKD, may prevent growth.