文章基本信息

标题：Loss of Polycystin-1 causes cAMP-dependent switch from tubule to cyst formation
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作者：Julia Katharina Scholz ; Andre Kraus ; Dominik Lüder 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：6
页码：1-17
DOI：10.1016/j.isci.2022.104359
语种：English
出版社：Elsevier
摘要：SummaryAutosomal dominant polycystic kidney disease is the most common monogenic disease that causes end-stage renal failure. It primarily results from mutations in the PKD1 gene that encodes for Polycystin-1. How loss of Polycystin-1 translates into bilateral renal cyst development is mostly unknown. cAMP is significantly involved in cyst enlargement but its role in cyst initiation has remained elusive. Deletion of Polycystin-1 in collecting duct cells resulted in a switch from tubule to cyst formation and was accompanied by an increase in cAMP. Pharmacological elevation of cAMP in Polycystin-1-competent cells caused cyst formation, impaired plasticity, nondirectional migration, and mis-orientation, and thus strongly resembled the phenotype of Polycystin-1-deficient cells. Mis-orientation of developing tubule cells in metanephric kidneys upon loss of Polycystin-1 was phenocopied by pharmacological increase of cAMP in wildtype kidneys.In vitro, cAMP impaired tubule formation after capillary-induced injury which was further impaired by loss Polycystin-1.Graphical abstractDisplay OmittedHighlights•Loss of Polycystin-1 switches renal cells from tubule to cyst formation•Deletion of Polycystin-1 leads to increase in cAMP•Elevation of cAMP in wildtype cells phenocopies Polycystin-1-deficient features•Features are: impaired plasticity, nondirectional migration, and mis-orientationNephrology; Machine learning.