title: MiR-107 induces TNF-α secretion in endothelial cells causing tubular cell injury in patients with septic acute kidney injury.
abstract: Activation of endothelial cells plays a key role in septic acute kidney injury (AKI). This study investigated the role of miRNA in endothelial-induced tubular cell injury in sepsis. Circulating endothelial cells (CECs) from septic AKI, non-septic AKI, septic non-AKI patients and healthy volunteers were isolated and cultured, and HK2 cells were exposed to CEC-conditioned medium. CEC-conditioned medium prepared from septic AKI patients led to cell shrinkage, decreased E-cadherin, the release of NAG and cell apoptosis in HK2 cells. TNF-α mediated the tubular cell injury induced by CEC-conditioned medium prepared from septic AKI patients. PCR array analysis detected that miR-107 was significantly increased in the CECs of septic AKI patients. MiR-107 was verified to target the 3'UTR of Dual-specificity phosphatase 7(DUSP7). Transfection of miR-107 ASO recovered the expression of DUSP7, suppressed the phosphorylation of ERK, and decreased the secretion of TNF-α in the CECs of septic AKI patients and in the peritubular endothelial cells of septic AKI mice. The inhibition of miR-107 prevented the decrease of E-cadherin, the release of NAG and cell apoptosis in HK2 cells exposed to CEC-conditioned medium prepared from septic AKI patients, and preserved the normal renal morphology and decreased the serum creatinine level in septic AKI mice. In conclusion, our study suggests that the increased miR-107 induces TNF-α secretion by targeting DUSP7 in endothelial cells, which may directly cause tubular cell injury in septic AKI.
authors.affiliation: Department of Emergency, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Emergency, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.
authors.forename: Zengdi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Emergency, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Emergency, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China. Electronic address: hongjunmiao@163.com.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Miao
mesh_terms: D020413:3' Untranslated Regions; D058186:Acute Kidney Injury / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D054637:Dual-Specificity Phosphatases / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000293:injuries / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D018805:Sepsis / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; C000611838:Cdh1 protein, mouse; D017077:Culture Media, Conditioned; C549045:MIRN107 microRNA, human; C555365:MIRN107 microRNA, mouse; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; C107523:DUSP7 protein, human; D054637:Dual-Specificity Phosphatases
keywords: Acute kidney injury; Endothelial cells; Sepsis; miRNA