Identification of ADPKD-Related Genes and Pathways in Cells Overexpressing PKD2

Consistent with the gene dosage effect hypothesis, renal cysts can arise in transgenic murine models overexpressing either or , which are causal genes for autosomal dominant polycystic kidney disease (ADPKD). To determine whether gene overexpression is a universal mechanism driving cystogenesis or i...

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Bibliographic Details
Published in:	Genes Vol. 11; no. 2; p. 122
Main Authors:	Zhang, Zhe, Dang, Yanna, Wang, Zizengceng, Wang, Huanan, Pan, Yuchun, He, Jin
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI 22-01-2020
Subjects:	Animals Apoptosis - genetics Cell Proliferation - genetics Cysts - genetics Cysts - metabolism Disease Models, Animal Kidney - pathology LLC-PK1 Cells Mice Mutation Polycystic Kidney, Autosomal Dominant - genetics Polycystic Kidney, Autosomal Dominant - metabolism Protein Kinases - genetics Protein Kinases - metabolism Swine Whole Exome Sequencing - methods RNA-seq PKD2 ADPKD
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Summary:	Consistent with the gene dosage effect hypothesis, renal cysts can arise in transgenic murine models overexpressing either or , which are causal genes for autosomal dominant polycystic kidney disease (ADPKD). To determine whether gene overexpression is a universal mechanism driving cystogenesis or is merely restricted to rodents, other animal models are required. Previously, we failed to observe any renal cysts in a transgenic porcine model of overexpression partially due to epigenetic silencing of the transgene. Thus, to explore the feasibility of porcine models and identify potential genes/pathways affected in ADPKD, LLC-PK1 cells with high expression were generated. mRNA sequencing (RNA-seq) was performed, and , , and were found to be upregulated genes common to the different overexpression cell models. is a well-characterized factor contributing to cystogenesis, and is a biomarker for chronic kidney disease. Thus, these genes might be indicators of disease progression. Additionally, some ADPKD-associated pathways, e.g., the mitogen-activated protein kinase (MAPK) pathway, were enriched in the cells. Moreover, gene ontology (GO) analysis demonstrated that proliferation, apoptosis, and cell cycle regulation, which are hallmarks of ADPKD, were altered. Therefore, our experiment identified some biomarkers or indicators of ADPKD, indicating that high expression would likely drive cystogenesis in future porcine models.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2073-4425 2073-4425
DOI:	10.3390/genes11020122