Cruzado, Josep Ma.Manonelles, AnnaRayego Mateos, SandraDoladé, NuriaAmaya-Garrido, AnaVarela, CristianGuiteras, RoserMosquera Mayo, José LuísJung, MichaelaCodina, SergiMartinez Valenzuela, LauraBordignon Draibe, JulianaCouceiro, CarlosVigués i Julià, FrancescMadrid, ÁlvaroFlorian, Maria CarolinaRuíz-Ortega, MartaSola Martínez, Anna2024-10-162024-10-162024-02-280085-2538https://hdl.handle.net/2445/215815Parietal 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.18 p.application/pdfengcc-by-nc-nd (c) Cruzado, Josep Ma. et al., 2024http://creativecommons.org/licenses/by-nc-nd/4.0/Cèl·lules epitelialsAnimalsProliferació cel·lularEpithelial cellsAnimalsCell proliferationinfo:eu-repo/semantics/article7461562024-10-16info:eu-repo/semantics/openAccess38428734