Analysis of Altered MicroRNA Expression Profiles in Proximal Renal Tubular Cells in Response to Calcium Oxalate Monohydrate Crystal Adhesion: Implications for Kidney Stone DiseaseReport as inadecuate




Analysis of Altered MicroRNA Expression Profiles in Proximal Renal Tubular Cells in Response to Calcium Oxalate Monohydrate Crystal Adhesion: Implications for Kidney Stone Disease - Download this document for free, or read online. Document in PDF available to download.

Background

Calcium oxalate monohydrate COM is the major crystalline component in kidney stones and its adhesion to renal tubular cells leads to tubular injury. However, COM-induced toxic effects in renal tubular cells remain ambiguous. MicroRNAs miRNAs play an important role in gene regulation at the posttranscriptional levels.

Objective

The present study aimed to assess the potential changes in microRNAs of proximal renal tubular cells in response to the adhesion of calcium oxalate monohydrate COM crystals.

Methodology

Lactate dehydrogenase LDH activity and DAPI staining were used to measure the toxic effects of HK-2 cells exposed to COM crystals. MicroRNA microarray and mRNA microarray were applied to evaluate the expression of HK-2 cells exposed to COM crystals. Quantitative real-time PCR qRT-PCR technology was used to validate the microarray results. Target prediction, Gene Ontology GO analysis and pathway analysis were applied to predict the potential roles of microRNAs in biological processes.

Principal Findings

Our study showed that COM crystals significantly altered the global expression profile of miRNAs in vitro. After 24 h treatment with a dose 1 mmol-L, 25 miRNAs were differentially expressed with a more than 1.5-fold change, of these miRNAs, 16 were up-regulated and 9 were down-regulated. A majority of these differentially expressed miRNAs were associated with cell death, mitochondrion and metabolic process. Target prediction and GO analysis suggested that these differentially expressed miRNAs potentially targeted many genes which were related to apoptosis, regulation of metabolic process, intracellular signaling cascade, insulin signaling pathway and type 2 diabetes.

Conclusion

Our study provides new insights into the role of miRNAs in the pathogenesis associated with nephrolithiasis.



Author: Bohan Wang, Bolin Wu, Jun Liu, Weimin Yao, Ding Xia, Lu Li, Zhiqiang Chen, Zhangqun Ye, Xiao Yu

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



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