Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, South Korea.
Hyonam Kidney Laboratory, Soonchunhyang University Seoul Hospital, 59 Daesagwan-ro, Youngsan-gu, Seoul, South Korea.
J Transl Med. 2019 Jul 22;17(1):236. doi: 10.1186/s12967-019-1983-3.
Diabetic nephropathy (DN) is associated with high risk of cardiovascular disease and mortality. Exosomal microRNAs (miRNAs) regulate gene expression in a variety of tissues and play important roles in the pathology of various diseases. We hypothesized that the exosomal miRNA profile would differ between DN patients and patients without nephropathy.
We prospectively enrolled 74 participants, including healthy volunteers (HVs), diabetic patients without nephropathy, and those with DN. The serum exosomal miRNA profiles of participants were examined using RNA sequencing.
The expression levels of 107 miRNAs differed between HVs and patients without DN, whereas the expression levels of 95 miRNAs differed between HVs and patients with DN. Among these miRNAs, we found 7 miRNAs (miR-1246, miR-642a-3p, let-7c-5p, miR-1255b-5p, let-7i-3p, miR-5010-5p, miR-150-3p) that were uniquely up-regulated in DN patients compared to HVs, and miR-4449 that was highly expressed in DN patients compared to patients without DN. A pathway analysis revealed that these eight miRNAs are likely involved in MAPK signaling, integrin function in angiogenesis, and regulation of the AP-1 transcription factor. Moreover, they were all significantly correlated with the degree of albuminuria.
Patients with DN have a different serum exosomal miRNA profile compared to HVs. These miRNAs may be promising candidates for the diagnosis and treatment of DN and cardiovascular disease.
糖尿病肾病（DN）与心血管疾病和死亡率的高风险相关。外泌体 microRNAs（miRNAs）在多种组织中调节基因表达，在各种疾病的病理中发挥重要作用。我们假设 DN 患者与无肾病患者的外泌体 miRNA 谱不同。
我们前瞻性地招募了 74 名参与者，包括健康志愿者（HV）、无肾病的糖尿病患者和 DN 患者。使用 RNA 测序检查参与者的血清外泌体 miRNA 谱。
HV 与无肾病患者之间的表达水平有 107 个 miRNAs 不同，HV 与 DN 患者之间的表达水平有 95 个 miRNAs 不同。在这些 miRNAs 中，我们发现 7 个 miRNAs（miR-1246、miR-642a-3p、let-7c-5p、miR-1255b-5p、let-7i-3p、miR-5010-5p、miR-150-3p）在 DN 患者中与 HV 相比特异性上调，miR-4449 在 DN 患者中与无肾病患者相比高度表达。通路分析表明，这 8 个 miRNAs 可能参与 MAPK 信号、血管生成中的整合素功能和 AP-1 转录因子的调节。此外，它们都与白蛋白尿程度显著相关。
与 HV 相比，DN 患者的血清外泌体 miRNA 谱不同。这些 miRNAs 可能是 DN 和心血管疾病诊断和治疗的有前途的候选物。
