Urine MicroRNA as Potential Biomarkers of Autosomal Dominant Polycystic Kidney Disease Progression: Description of miRNA Profiles at BaselineReport as inadecuate




Urine MicroRNA as Potential Biomarkers of Autosomal Dominant Polycystic Kidney Disease Progression: Description of miRNA Profiles at Baseline - Download this document for free, or read online. Document in PDF available to download.

Background

Autosomal dominant polycystic kidney disease ADPKD is clinically heterogenic. Biomarkers are needed to predict prognosis and guide management. We aimed to profile microRNA miRNA in ADPKD to gain molecular insight and evaluate biomarker potential.

Methods

Small-RNA libraries were generated from urine specimens of ADPKD patients N = 20 and patients with chronic kidney disease of other etiologies CKD, N = 20. In this report, we describe the miRNA profiles and baseline characteristics. For reference, we also examined the miRNA transcriptome in primary cultures of ADPKD cyst epithelia N = 10, normal adult tubule N = 8 and fetal tubule N = 7 epithelia.

Results

In primary cultures of ADPKD kidney cells, miRNA cistrons mir-1432 9.2-fold, let-7i1 2.3-fold and mir-36191 12.1-fold were significantly elevated compared to normal tubule epithelia, whereas mir-14 members 19.7-fold, mir-133b2 21.1-fold and mir-2051 3.0-fold were downregulated P<0.01. Expression of the dysregulated miRNA in fetal tubule epithelia resembled ADPKD better than normal adult cells, except let-7i, which was lower in fetal cells. In patient biofluid specimens, mir-1432 members were 2.9-fold higher in urine cells from ADPKD compared to other CKD patients, while expression levels of mir-133b2 4.9-fold and mir-14 4.4-fold were lower in ADPKD. We also noted increased abundance mir-2231 5.6-fold, mir-199a3 1.4-fold and mir-199b1 1.8-fold P<0.01 in ADPKD urine cells. In ADPKD urine microvesicles, miR-12 7.2-fold and miR-133a2 11.8-fold were less abundant compared to other CKD patients P<0.01.

Conclusions

We found that in ADPKD urine specimens, miRNA previously implicated as kidney tumor suppressors miR-1 and miR-133, as well as miRNA of presumed inflammatory and fibroblast cell origin miR-223-miR-199, are dysregulated when compared to other CKD patients. Concordant with findings in the primary tubule epithelial cell model, this suggests roles for dysregulated miRNA in ADPKD pathogenesis and potential use as biomarkers. We intend to assess prognostic potential of miRNA in a followup analysis.



Author: Iddo Z. Ben-Dov , Ying-Cai Tan, Pavel Morozov, Patricia D. Wilson, Hanna Rennert, Jon D. Blumenfeld, Thomas Tuschl

Source: http://plos.srce.hr/



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