MicroRNA-150 deletion in mice protects kidney from myocardial infarction-induced acute kidney injury

Punithavathi Ranganathan, Calpurnia Jayakumar, Yaoping Tang, Kyoung Mi Park, Jian Peng Teoh, Huabo Su, Jie Li, Il Man Kim, Ganesan Ramesh

Research output: Contribution to journalArticle

29 Scopus citations

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 insulinlike 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.

Original languageEnglish (US)
Pages (from-to)F551-F558
JournalAmerican Journal of Physiology - Renal Physiology
Volume309
Issue number6
DOIs
Publication statusPublished - Sep 15 2015

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Keywords

  • Acute kidney injury
  • Bilateral renal pedicle clamping model
  • MiR-150
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Urology

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