title: MicroRNA-150 deletion in mice protects kidney from myocardial infarction-induced acute kidney injury.
abstract: Despite greater understanding of acute kidney injury (AKI) in animal models, many of the preclinical studies are not translatable. Most of the data were derived from a bilateral renal pedicle clamping model with warm ischemia. However, ischemic injury of the kidney in humans is distinctly different and does not involve clamping of renal vessel. Permanent ligation of the left anterior descending coronary artery model was used to test the role of microRNA (miR)-150 in AKI. Myocardial infarction in this model causes AKI which is similar to human cardiac bypass surgery. Moreover, the time course of serum creatinine and biomarker elevation were also similar to human ischemic injury. Deletion of miR-150 suppressed AKI which was associated with suppression of inflammation and interstitial cell apoptosis. Immunofluorescence staining with endothelial marker and marker of apoptosis suggested that dying cells are mostly endothelial cells with minimal epithelial cell apoptosis in this model. Interestingly, deletion of miR-150 also suppressed interstitial fibrosis. Consistent with protection, miR-150 deletion causes induction of its target gene insulin-like growth factor-1 receptor (IGF-1R) and overexpression of miR-150 in endothelial cells downregulated IGF-1R, suggesting miR-150 may mediate its detrimental effects through suppression of IGF-1R pathways.
authors.affiliation: Department of Medicine and Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
authors.forename: Punithavathi
authors.initials: P
authors.lastname: Ranganathan
authors.affiliation: Department of Medicine and Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
authors.forename: Calpurnia
authors.initials: C
authors.lastname: Jayakumar
authors.affiliation: Department of Medicine and Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
authors.forename: Yaoping
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Medicine and Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
authors.forename: Kyoung-mi
authors.initials: KM
authors.lastname: Park
authors.affiliation: Department of Medicine and Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
authors.forename: Jian-peng
authors.initials: JP
authors.lastname: Teoh
authors.affiliation: Department of Medicine and Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
authors.forename: Huabo
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Medicine and Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medicine and Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
authors.forename: Il-man
authors.initials: IM
authors.lastname: Kim
authors.affiliation: Department of Medicine and Vascular Biology Center, Georgia Regents University, Augusta, Georgia gramesh@gru.edu.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Ramesh
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D017353:Gene Deletion; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D009203:Myocardial Infarction / Q000150:complications* / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000473:pathology
chemical_list: D035683:MicroRNAs; C529101:Mirn150 microRNA, mouse; D017526:Receptor, IGF Type 1
keywords: acute kidney injury; bilateral renal pedicle clamping model; miR-150; myocardial infarction