Downregulation of hsa-miR-100-5p May Be a Protective Factor in the Early Stages of Nephropathy in Type 1 Diabetes Mellitus

Author:

Pinheiro Andrey Henrique Gama1ORCID,Pereira Beatriz de Oliveira1,Silva Lilian Souza D’Albuquerque2,Melo Franciane T. Cunha de2,Souza Ana Carolina C. Braga de2,Leal Valéria S. Galvão2,Figueiredo Priscila B. Barbosa de2ORCID,Neto João F. Abrahão2,Santos Marcia Costa dos2,Queiroz Natércia Neves Marques de2,Felício Karem Miléo2,Ribeiro-dos-Santos Ândrea1ORCID,Felício João Soares2,Cavalcante Giovanna C.1ORCID

Affiliation:

1. Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Pará, Belém 66075-110, PA, Brazil

2. Endocrinology and Metabology/Diabetes Unit, João de Barros Barreto University Hospital, Federal University of Pará, Belém 66075-110, PA, Brazil

Abstract

Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Fundação Amazônia de Amparo a Estudos e Pesquisas

Pró-Reitoria de Pesquisa e Pós-Graduação da Universidade Federal do Pará

Rede de Pesquisa em Genômica Populacional Humana

CNPq/MCTI/FNDCT—Processo

Publisher

MDPI AG

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