Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Pará, Belém 66075-110, PA, Brazil.
Endocrinology and Metabology/Diabetes Unit, João de Barros Barreto University Hospital, Federal University of Pará, Belém 66075-110, PA, Brazil.
Int J Mol Sci. 2024 May 23;25(11):5663. doi: 10.3390/ijms25115663.
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.
1 型糖尿病(T1DM)可导致严重并发症,如糖尿病肾病(DKD)或糖尿病肾病(DN),它已成为全球终末期(终末期)肾病的主要原因。对于 T1DM,DKD 的临床评估使用肾小球滤过率(GFR)和尿白蛋白排泄(UAE)等标志物。然而,DKD 的早期诊断仍然是一个挑战。因此,研究分子标志物,如 microRNAs(miRNAs),为早期诊断提供了一个有前途的视角,突出了其稳定性和反映早期分子表现的能力。因此,在这里,我们研究了四种 miRNAs(hsa-let-7i-5p、hsa-miR-143-3p、hsa-miR-501-3p 和 hsa-miR-100-5p)与 T1DM 患者的肾病,将白蛋白尿(微白蛋白尿和白蛋白尿)作为评估组的标准。结果,我们发现 MIC 患者 miR-100-5p 的表达降低,表明其在肾病中具有保护作用。除此之外,当比较 miRNA miR-501-3p 和 miR-143-3p 时,各组(非 UAE 与 UAE)之间的表达水平没有差异。最后,miR-143-3p 和 miR-100-5p 与 AKT1、MMP13 和 IGF1R 等一些靶基因相关,这些基因与信号通路和细胞代谢有关。