Serum microRNA profiles in patients with autosomal dominant polycystic kidney disease show systematic dysregulation partially reversible by hemodialysis

Abstract

Introduction: The impact of autosomal dominant polycystic kidney disease (ADPKD) on serum microRNAs (miRNA) is unknown. Material and methods: For profiling experiment we recruited 30 patients from three equinumerous groups: controls, ADPKD and ADPKD on hemodialysis. From the last group extra samples were collected for in pre-/post-dialysis analysis. Additionally, 23 healthy volunteers were used for selected biomarker verification. Real-time PCR arrays were used for quantification of 752 miRNAs. Validation of selected miRNAs was performed in total RNA extracted from the serum and the exosomal fraction in pre-/post-dialysis samples. Results: In total, 37 significant circulating miRNAs were found to differ between ADPKD patients and controls. In validation, 3 miRNAs with the highest fold change in comparison of dialyzed vs non-dialyzed patients (miR-532-3p, miR-320b, miR-144-5p) were not significantly altered by hemodialysis and from the top down-regulated ones, miR-27a-3p was significantly lower after dialysis in both total and exosomal fractions, miR-20a-5p was down-regulated in the exosomal fraction and miR-16-5p was unaltered by hemodialysis. MiR-16-5p was selected as the best circulating biomarker of ADPKD. Circulating representatives of the miR-17 family sharing the same seed region (miR-20a-5p, miR-93-5p and miR-106a-5p) showed significantly lower expression among dialyzed vs. non-dialyzed patients and their exosomal fraction dropped after hemodialysis. Conclusions: The serum miRNAs among ADPKD patients differ substantially depending on the stage of CKD. The exosomal fraction of miRNA was more affected by dialysis than the total one. There was a common pattern of down-regulation for circulating miR-17 family members sharing the same seed region.

MiR-423-5p as Optimal Endogenous Control for Quantification of Circulating MicroRNAs in Patients With CKD

“…First, we retrieved a publicly available miRNA data set investigating serum miRNA profiles in patients with autosomal dominant polycystic kidney disease from Gene Expression Omnibus Repository (GSE101811) for analysis. 3 This study included 10 healthy controls, 10 nondialysis-dependent and 10 dialysis-dependent patients with autosomal dominant polycystic kidney disease. A total of 752 miRNAs plus control assays were quantified using the miRCURY LNA ExiqonRT-PCR human miRNA arrays I and II (Exiqon, Copenhagen, Denmark).…”

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases

“…For instance, miR-30a-5p, miR-30d-5p, miR-30e-5p, miR-192-5p, and miR-194-5p exhibited notable downregulation in patients' exosomes, murine Pkd1 cystic kidneys, and human PKD1 cystic kidney tissue [126]. Similarly, miR-20a, miR-93-5p, and miR-106a-5p were detected as downregulated in serum samples from ADPKD patients who had undergone dialysis [127]. Altogether, these studies indicate that such miRNAs could be used as biomarkers and further studied for the development of miRNA-based drugs against ADPKD.…”

miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis

“…In addition, miR-16-5p plays a significant role in the kidney and is involved in the occurrence and development of a variety of kidney diseases. In autosomal dominant polycystic kidney disease (ADPKD), miR-16-5p showed significant differences and was selected as the best circulating biomarker for ADPKD [ 15 ]. Duan et al.…”