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

Punithavathi Ranganathan, Calpurnia Jayakumar, Yao Liang Tang, Kyoung Mi Park, Jian Peng Teoh, Huabo Su, Jie Li, Il-man Kim, Ganesan Ramesh

Research output: Contribution to journalArticle

21 Citations (Scopus)

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
StatePublished - Sep 15 2015

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MicroRNAs
Acute Kidney Injury
Myocardial Infarction
Kidney
Growth Factor Receptors
Apoptosis
Constriction
Endothelial Cells
Warm Ischemia
Wounds and Injuries
Thoracic Surgery
Fluorescent Antibody Technique
Ligation
Creatinine
Coronary Vessels
Fibrosis
Down-Regulation
Animal Models
Biomarkers
Epithelial Cells

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

MicroRNA-150 deletion in mice protects kidney from myocardial infarction-induced acute kidney injury. / Ranganathan, Punithavathi; Jayakumar, Calpurnia; Tang, Yao Liang; Park, Kyoung Mi; Teoh, Jian Peng; Su, Huabo; Li, Jie; Kim, Il-man; Ramesh, Ganesan.

In: American Journal of Physiology - Renal Physiology, Vol. 309, No. 6, 15.09.2015, p. F551-F558.

Research output: Contribution to journalArticle

Ranganathan, Punithavathi ; Jayakumar, Calpurnia ; Tang, Yao Liang ; Park, Kyoung Mi ; Teoh, Jian Peng ; Su, Huabo ; Li, Jie ; Kim, Il-man ; Ramesh, Ganesan. / MicroRNA-150 deletion in mice protects kidney from myocardial infarction-induced acute kidney injury. In: American Journal of Physiology - Renal Physiology. 2015 ; Vol. 309, No. 6. pp. F551-F558.
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