title: Analysis of altered microRNA expression profiles in proximal renal tubular cells in response to calcium oxalate monohydrate crystal adhesion: implications for kidney stone disease.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our study provides new insights into the role of miRNAs in the pathogenesis associated with nephrolithiasis.
authors.affiliation: Department of Urinary Surgery, Affiliated Second Hospital of Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Bohan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Urinary Surgery, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Bolin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Urinary Surgery, Suining Centre Hospital, Suining, Sichuan Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urinary Surgery, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Urinary Surgery, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Xia
authors.affiliation: Department of Urinary Surgery, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Urinary Surgery, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Urinary Surgery, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Urinary Surgery, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002129:Calcium Oxalate / Q000633:toxicity*; D002460:Cell Line; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D002129:Calcium Oxalate