The role of the tricellular junction protein ILDR2 in glomerulopathies: Expression patterns and functional insights

Abstract

The tricellular tight junctions are crucial for the regulation of paracellular flux at tricellular junctions, where tricellulin (MARVELD2) and angulins (ILDR1, ILDR2, or LSR) are localized. The role of ILDR2 in podocytes, specialized epithelial cells in the kidney, is still unknown. We investigated the role of ILDR2 in glomeruli and its influence on blood filtration. Western blots, single-cell RNA sequencing (scRNA-seq), and superresolution microscopy showed a strong expression of ILDR2 in podocytes that colocalized with the podocyte-specific claudin CLDN5. Co-immunoprecipitation revealed that ILDR2 interacts with CLDN5. In glomerulopathies, induced by nephrotoxic serum and by desoxycorticosterone acetate (DOCA)-salt heminephrectomy, ILDR2 was strongly up-regulated. Furthermore, Ildr2 knockout mice exhibited glomerular hypertrophy and decreased podocyte density. However, they did not develop effacement of podocyte foot processes or proteinuria. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis of isolated glomeruli showed an increase in matrix proteins, such as fibronectin and collagens. This suggests a protective role of ILDR2 in glomerulopathies. mehr

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Titel	The role of the tricellular junction protein ILDR2 in glomerulopathies: Expression patterns and functional insights
Medien	iScience
Heft	12
Band	27
ISSN	2589-0042
Verfasser	Florian Siegerist, Felix Kliewe, Elke Hammer, Paul Schakau, Joanne Chi Soh, Claudia Weber, Maja Lindenmeyer, Simone Reichelt-Wurm, Vedran Drenic, Christos Chatziantoniou, Christos Chadjichristos, Yiying Zhang, Prof. Dr. Stefan Simm, Miriam Banas, Matthias Nauck, Uwe Völker, Nicole Endlich
Seiten	111329
Veröffentlichungsdatum	12.2024
Zitation	Siegerist, Florian; Kliewe, Felix; Hammer, Elke; Schakau, Paul; Chi Soh, Joanne; Weber, Claudia; Lindenmeyer, Maja; Reichelt-Wurm, Simone; Drenic, Vedran; Chatziantoniou, Christos; Chadjichristos, Christos; Zhang, Yiying; Simm, Stefan; Banas, Miriam; Nauck, Matthias; Völker, Uwe; Endlich, Nicole (2024): The role of the tricellular junction protein ILDR2 in glomerulopathies: Expression patterns and functional insights. iScience 27 (12), 111329. DOI: 10.1016/j.isci.2024.111329