Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Integrated miRNA–mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy

Marina López-Martínez
,
Maria Pilar Armengol
,
Irina Pey
,
Xavi Farré
,
Paula Rodríguez-Martínez
,
Mieria Ferrer
,
Esteban Porrini
,
Sergio Luis-Lima
,
Laura Diaz-Martin
,
Ana Elena Rodríguez-Rodríguez
ORCID logo ,
Coriolano Cruz-Perera
,
Marta Alcalde
,
Maruja Navarro-Díaz
* ORCID logo
Version 1 : Received: 2 May 2024 / Approved: 3 May 2024 / Online: 3 May 2024 (09:36:57 CEST)

How to cite: López-Martínez, M.; Armengol, M. P.; Pey, I.; Farré, X.; Rodríguez-Martínez, P.; Ferrer, M.; Porrini, E.; Luis-Lima, S.; Diaz-Martin, L.; Rodríguez-Rodríguez, A. E.; Cruz-Perera, C.; Alcalde, M.; Navarro-Díaz, M. Integrated miRNA–mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy. Preprints 2024, 2024050183. https://doi.org/10.20944/preprints202405.0183.v1 López-Martínez, M.; Armengol, M. P.; Pey, I.; Farré, X.; Rodríguez-Martínez, P.; Ferrer, M.; Porrini, E.; Luis-Lima, S.; Diaz-Martin, L.; Rodríguez-Rodríguez, A. E.; Cruz-Perera, C.; Alcalde, M.; Navarro-Díaz, M. Integrated miRNA–mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy. Preprints 2024, 2024050183. https://doi.org/10.20944/preprints202405.0183.v1

Abstract

This study aimed to investigates obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: control (n=15) and study groups (n=15) that were fed a standard (SD) and high-fat diet (HFD), respectively. After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD group exhibited increased weight gain (55.8% vs 29.2%; P< 0.001) and albuminuria (10384.04 ng/ml vs 5845.45 ng/ml; P<0.001) compared to controls. The HFD group exhibited early stages of ORG lesions, with a predominance of mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that four DE miRNAs in the kidneys of the HFD group negatively regulated the PTEN gene, which promotes podocyte endocytosis of lipids in ORG. Among these four miRNAs, miR-205 was upregulated in the urine of the HFD group. HFD-fed Wistar rats developed early stages of ORG, with a specific targetome of miRNAs and gene expression. The upregulation of miR-205 in the kidney and its isolation in urine are associated with lipid endocytosis in podocytes, which could become a plausible biomarker of the early stages of ORG and lead to future therapeutic research.

Keywords

microRNA; biomarker; targetome; obesity-related glomerulopathy; mesangial matrix increase; podocyte hypertrophy; Wistar rats

Subject

Public Health and Healthcare, Public Health and Health Services

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.