Integrated miRNA-mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy
López-Martínez, Marina (Hospital Universitari Vall d'Hebron)
Armengol Barnils, Maria del Pilar (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pey, Irina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Farré Ramon, Xavier (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rodriguez Martinez, Paula (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ferrer, Mireia (Vall d'Hebron Institut de Recerca (VHIR))
Porrini, Esteban (Universidad de La Laguna)
Luis-Lima, Sergio (Universidad de La Laguna)
Díaz-Martín, Laura (Universidad de La Laguna)
Rodríguez-Rodríguez, Ana Elena (Universidad de La Laguna)
Cruz-Perera, Coriolano (Universidad de La Laguna)
Alcalde-Herraiz, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Navarro Díaz, Maruja (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Date:	2024
Abstract:	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.
Grants:	Instituto de Salud Carlos III PI18-01951
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	MicroRNA ; Biomarker ; Targetome ; Obesity-related glomerulopathy ; Mesangial matrix ; Increase ; Podocyte hypertrophy ; Wistar rats
Published in:	International journal of molecular sciences, Vol. 25, Núm. 12 (June 2024) , ISSN 1422-0067

DOI: 10.3390/ijms25126437
PMID: 38928144

21 p, 7.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles