Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis.

Autor:	Cruzado JM; Department of Nephrology and Transplantation, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain; Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain., Manonelles A; Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain., Rayego-Mateos S; Cellular Biology in Renal Diseases Laboratory, IIS Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain., Doladé N; Department of Nephrology and Transplantation, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain., Amaya-Garrido A; Department of Nephrology and Transplantation, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain., Varela C; Department of Nephrology and Transplantation, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain., Guiteras R; Department of Nephrology and Transplantation, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain., Mosquera JL; Department of Nephrology and Transplantation, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain., Jung M; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt am Main, Germany., Codina S; Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain., Martínez-Valenzuela L; Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain., Draibe J; Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain., Couceiro C; Department of Nephrology and Transplantation, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain; Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain., Vigués F; Department of Urology, Hospital Universitari Bellvitge, Barcelona, Spain., Madrid Á; Pediatric Nephrology Department, Sant Joan de Deu University Hospital, Barcelona, Spain., Florian MC; Program of Regenerative Medicine, The Bellvitge Institute for Biomedical Research (IDIBELL), Barcelona, Spain; Stem Cell Aging Group, Regenerative Medicine Program, The Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; The Catalan Institution for Research and Advanced Studies (ICREA)., Ruíz-Ortega M; Cellular Biology in Renal Diseases Laboratory, IIS Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain., Sola A; Department of Nephrology and Transplantation, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain. Electronic address: asola@idibell.cat.
Jazyk:	angličtina
Zdroj:	Kidney international [Kidney Int] 2024 Jul; Vol. 106 (1), pp. 67-84. Date of Electronic Publication: 2024 Feb 28.
DOI:	10.1016/j.kint.2024.02.010
Abstrakt:	Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. Here, we found that CSF-1R was upregulated in PECs and podocytes in biopsies from patients with FSGS. Through in vitro studies, PECs were found to constitutively express CSF-1R. Incubation with CSF-1 induced CSF-1R upregulation and significant transcriptional regulation of genes involved in pathways associated with PEC activation. Specifically, CSF-1/CSF-1R activated the ERK1/2 signaling pathway and upregulated CD44 in PECs, while both ERK and CSF-1R inhibitors reduced CD44 expression. Functional studies showed that CSF-1 induced PEC proliferation and migration, while reducing the differentiation of PECs into podocytes. These results were validated in the Adriamycin-induced FSGS experimental mouse model. Importantly, treatment with either the CSF-1R-specific inhibitor GW2580 or Ki20227 provided a robust therapeutic effect. Thus, we provide evidence of the role of the CSF-1/CSF-1R pathway in PEC activation in FSGS, paving the way for future clinical studies investigating the therapeutic effect of CSF-1R inhibitors on patients with FSGS. (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu