title: Differentially expressed miRNAs in sepsis-induced acute kidney injury target oxidative stress and mitochondrial dysfunction pathways.
abstract: OBJECTIVE
  To identify specific miRNAs involved in sepsis-induced AKI and to explore their targeting pathways.
  
  
  METHODS
  The expression profiles of miRNAs in serum from patients with sepsis-induced AKI (n = 6), sepsis-non AKI (n = 6), and healthy volunteers (n = 3) were investigated by microarray assay and validated by quantitative PCR (qPCR). The targets of the differentially expressed miRNAs were predicted by Target Scan, mirbase and Miranda. Then the significant functions and involvement in signaling pathways of gene ontology (GO) and KEGG pathways were analyzed. Furthermore, eight miRNAs were randomly selected out of the differentially expressed miRNAs for further testing by qPCR.
  
  
  RESULTS
  qPCR analysis confirmed that the expressions levels of hsa-miR-23a-3p, hsa-miR-4456, hsa-miR-142-5p, hsa-miR-22-3p and hsa-miR-191-5p were significantly lower in patients with sepsis compared with the healthy volunteers, while hsa-miR-4270, hsa-miR-4321, hsa-miR-3165 were higher in the sepsis patients. Statistically, miR-4321; miR-4270 were significantly upregulated in the sepsis-induced AKI compared with sepsis-non AKI, while only miR-4321 significantly overexpressed in the sepsis groups compared with control groups. GO analysis showed that biological processes regulated by the predicted target genes included diverse terms. They were related to kidney development, regulation of nitrogen compound metabolic process, regulation of cellular metabolic process, cellular response to oxidative stress, mitochondrial outer membrane permeabilization, etc. Pathway analysis showed that several significant pathways of the predicted target genes related to oxidative stress. miR-4321 was involved in regulating AKT1, mTOR and NOX5 expression while miR-4270 was involved in regulating PPARGC1A, AKT3, NOX5, PIK3C3, WNT1 expression. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in oxidative stress and mitochondrial dysfunction.
  
  
  CONCLUSIONS
  This study might help to improve understanding of the relationship between serum miRNAs and sepsis-induced AKI, and laid an important foundation for further identification of the potential mechanisms of sepsis-induced AKI and oxidative stress and mitochondrial dysfunction.
authors.affiliation: Department of Emergency, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qin-Min
authors.initials: QM
authors.lastname: Ge
authors.affiliation: Department of Emergency, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Huang
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, United States of America.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Bian
authors.affiliation: Department of Emergency, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Pan
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000235:genetics*; D000368:Aged; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D060888:Real-Time Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications / Q000235:genetics*
chemical_list: D016207:Cytokines; D035683:MicroRNAs