Urinary exosomal microRNA panel unravels novel biomarkers for diagnosis of type 2 diabetic kidney disease

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• 作者：Sanaa Eissa^a ; ^{Dr_sanaa_eissa@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; ^{Drsanaa_mohamed@med.asu.edu.eg" class="auth_mail" title="E-mail the corresponding author} ; Marwa Matboli^a ; Rowaida Aboushahba^a ; Miram M. Bekhet^b ; Yasser Soliman^c
• 关键词：miRNA ; Diabetic kidney disease ; Exosomes ; Urinary biomarkers ; Diagnostics
• 刊名：Journal of Diabetes and its Complications
• 出版年：2016
• 出版时间：November-December 2016
• 年：2016
• 卷：30
• 期：8
• 页码：1585-1592
• 全文大小：627 K

文摘

A potential approach adopted in the current study is to design a panel based on in silico retrieval of novel miRNAs related to diabetic kidney disease and to evaluate its usefulness in disease diagnosis.

Patient and Methods

In the current study, we measured the differential expression of a 6 miRNA panel in urine pellet and exosome in an initial screening group using syber green-based PCR array. Also, we performed pathway enrichment analysis of the key target genes of these miRNAs. Finally, we selected the most significantly up-regulated miRNAs in DKD, exosomal miR-15b, miR-34a and miR-636, that were measured by real-time PCR in a larger independent set of 180 participants to evaluate their usefulness as novel urine biomarkers for diagnosis diabetic kidney disease.

Results

PCR array analysis showed that miR-15b, miR-34a, and miR-636 were upregulated in both urine pellet and exosome of type 2DKD patients. qRT-PCR validation in the larger independent set of participants confirmed the significant up-regulation of these urinary exosomal miRs (P < 0.001). Notably, a positive correlation was found between these miRs, serum creatinine and urinary protein creatinine ratio. The sensitivity of this miRs based panel in urine exosomes reached 100% in diagnosis of DKD.

Conclusion

We identified urinary exosomal miR-15b, miR-34a, and miR-636 as a novel diagnostic panel and a major contributor in the pathogenesis of diabetic kidney disease.