Urinary exosome-derived microRNAs reflecting the changes of renal function and histopathology in dogs.
Urinary exosome-derived microRNAs reflecting the changes of renal function and histopathology in dogs.
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DOI：
10.1038/srep40340
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发表时间：
2017-01-11
影响因子：
4.6
通讯作者：
Kon Y
中科院分区：
文献类型：
--
作者：
Ichii O;Ohta H;Horino T;Nakamura T;Hosotani M;Mizoguchi T;Morishita K;Nakamura K;Hoshino Y;Takagi S;Sasaki N;Takiguchi M;Sato R;Oyamada K;Kon Y
MicroRNAs作为转录后调节因子，尿外切体(UExo)来源的microRNAs可作为生物标志物。在这里，我们筛选出反映狗肾脏疾病(KD)状态的UExo来源的microRNAs。受检犬按肾功能不同分为肾功能正常对照组(HC)和KD组。我们通过免疫印迹检测外显体标记TSG101和CD9，证实了UExo在狗身上出现了不规则的球形。根据我们先前使用KD模型小鼠的数据和本文通过对狗UExo来源的microRNAs的下一代测序获得的数据，miR-26a、miR-146a、miR-486、miR-21a和miR-10a/b被选为候选microRNAs。特别是，KD犬UExo来源的miR-26a和miR-10a/b显著降低，与其他miRNA相比，miR-26a水平与肾功能恶化呈负相关。在UExo、miR-26a和miR-191中，UExo来源的miR-21a水平是否校正为内部对照microRNA的水平，随着肾功能障碍的发生而显著增加。在肾组织中，肾小球miR-26a、miR-10a/b和肾小管间质miR-10b的表达下降与肾功能和组织病理学的恶化呈负相关。MiR-21a在肾小管间质而不是肾小球中的增加与肾组织病理学的恶化有关。综上所述，本研究鉴定了反映犬肾功能和组织病理学变化的microRNAs。
MicroRNAs act as post-transcriptional regulators, and urinary exosome (UExo)-derived microRNAs may be used as biomarkers. Herein, we screened for UExo-derived microRNAs reflecting kidney disease (KD) status in dogs. Examined dogs were divided into healthy kidney control (HC) and KD groups according to renal dysfunction. We confirmed the appearance of UExo having irregular globe-shapes in a dog by immunoblot detection of the exosome markers, TSG101 and CD9. Based on our previous data using KD model mice and the data obtained herein by next generation sequencing of UExo-derived microRNAs in dogs, miR-26a, miR-146a, miR-486, miR-21a, and miR-10a/b were selected as candidate microRNAs. In particular, UExo-derived miR-26a and miR-10a/b were significantly decreased in KD dogs, and miR-26a levels negatively correlated with deteriorated renal function compared to the other miRNAs. UExo-derived miR-21a levels corrected or not to that of internal control microRNAs in UExo, miR-26a and miR-191, significantly increased with renal dysfunction. In kidney tissues, the decrease of miR-26a and miR-10a/b in the glomerulus and miR-10b in the tubulointerstitium negatively correlated with deteriorated renal function and histopathology. Increased miR-21a in the tubulointerstitium rather than in the glomerulus correlated with deteriorated renal histopathology. In conclusion, microRNAs reflecting the changes in renal function and histopathology in dogs were identified in this study.