Loss of Polycystin-1 causes cAMP-dependent switch from tubule to cyst formation.

Scholz J, Kraus A, Lueder D, Skoczynski K, Schiffer M, Grampp S, Schödel J, Buchholz B (2022)

Publication Type: Journal article

Publication year: 2022

Journal

iScience Elsevier

Book Volume: 25

Journal Issue: 6

DOI: 10.1016/j.isci.2022.104359

Abstract

Autosomal 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.

Authors with CRIS profile

Julia Scholz Medizinische Fakultät Andre Kraus Department of Medicine 4 – Nephrology and Hypertension Kathrin Skoczynski Professur für Zellbiologie Mario Schiffer Lehrstuhl für Innere Medizin IV Steffen Grampp Department of Medicine 4 – Nephrology and Hypertension Johannes Schödel Department of Medicine 4 – Nephrology and Hypertension Björn Buchholz Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

Technische Hochschule Mittelhessen - University of Applied Sciences DE Germany (DE)

How to cite

APA:

Scholz, J., Kraus, A., Lueder, D., Skoczynski, K., Schiffer, M., Grampp, S.,... Buchholz, B. (2022). Loss of Polycystin-1 causes cAMP-dependent switch from tubule to cyst formation. iScience, 25(6). https://doi.org/10.1016/j.isci.2022.104359

MLA:

Scholz, Julia, et al. "Loss of Polycystin-1 causes cAMP-dependent switch from tubule to cyst formation." iScience 25.6 (2022).

BibTeX: Download