Sistema de Salut de Catalunya
Institut Català de la Salut
[López-Martínez M] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Armengol MP, Pey I, Farré X] Genomic Platform, Germans Trias i Pujol’s Research Institute, Badalona, Barcelona, Spain. [Rodríguez-Martínez P] Pathology Department, Germans Trias i Pujol Hospital, Badalona, Barcelona, Spain. [Ferrer M] Unitat d’Estadística i Bioinformàtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2024-07-04T06:28:35Z
2024-07-04T06:28:35Z
2024-06-11
Wistar rats; MicroRNA; Glomerulopathy
Rates Wistar; MicroARN; Glomerulopatia
Ratas Wistar; MicroARN; Glomerulopatía
This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.
This research was funded by Instituto de Salud Carlos III, grant number PI18-01951.
Article
Published version
English
MicroARN; Dieta; Obesitat; Ronyons - Malalties - Aspectes genètics; DISEASES::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases; Other subheadings::Other subheadings::Other subheadings::/genetics; PHENOMENA AND PROCESSES::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Overweight::Obesity; PHENOMENA AND PROCESSES::Physiological Phenomena::Diet, Food, and Nutrition::Nutritional Physiological Phenomena::Diet::Diet, High-Fat; CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs; ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales; Otros calificadores::Otros calificadores::Otros calificadores::/genética; FENÓMENOS Y PROCESOS::fenómenos fisiológicos::constitución corporal::pesos y medidas corporales::tamaño corporal::peso corporal::sobrepeso::obesidad; FENÓMENOS Y PROCESOS::fenómenos fisiológicos::dieta, alimentación y nutrición::fenómenos fisiológicos nutricionales::dieta::alimentación rica en grasa; COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN
MDPI
International Journal of Molecular Sciences;25(12)
https://doi.org/10.3390/ijms25126437
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - VHIR [1655]
