Severe ischemia-reperfusion injury induces epigenetic inactivation of LHX1 in kidney progenitor cells after kidney transplantation
Year: 2024
Type: article
Abstract: Severe ischemia-reperfusion injury (IRI) causes acute and chronic kidney allograft damage. As therapeutic interventions to reduce damage are limited yet, research on how to promote kidney repair has gained significant interest. To address this question, we performed genome-wide transcriptome and epigenome profiling in progenitor cells isolated from the urine of deceased (severe IRI) and living (mild IRI) donor human kidney transplants and identified LIM homeobox-1 (LHX1) as an epigenetically regulated gene whose expression depends on the IRI severity. Using a mouse model of IRI, we observed a relationship between IRI severity, LHX1 promoter hypermethylation, and LHX1 gene expression. Using functional studies, we confirmed that LHX1 expression is involved in the proliferation of epithelial tubular cells and podocyte differentiation from kidney progenitor cells. Our results provide evidence that severe IRI may reduce intrinsic mechanisms of kidney repair through epigenetic signaling.
Authors: Josep M. Cruzado, Anna Sola, Miguel L. Pato, Anna Manonelles, Cristian Varela, Fernando E. Setién, Carlos Quero-Dotor, James S. Heald, David Piñeyro, Ana Amaya-Garrido, Núria Doladé, Sergi Codina, Carlos Couceiro, Núria Bolaños, Montserrat Gomà, Francesc Vigués, Angelika Merkel, Paola Romagnani, María Berdasco
Institutions: Bellvitge University Hospital, Institut d'Investigació Biomédica de Bellvitge, Universitat de Barcelona, Meyer Children's Hospital, University of Florence, Josep Carreras Leukaemia Research Institute, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red de Cáncer
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,300
Awards: G1791132035, G2854544501, G4022723184, G425816975, G5123827200, Células parietales de la cápsula de Bowman (PECs), regeneración y daño en el trasplante renal. Identificación de dianas terapéuticas y terapia celular con PECs en isquemia-reperfusión, BLOQUEO DEL SRAA EN PACIENTES TRASPLANTADOS RENALES CON PRESENCIA DE PECs EN ORINA: ENSAYO CLÍNICO ALEATORIZADO DE VALSARTAN VERSUS PLACEBO
OpenAlex ID: W4404147584