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Deregulation of miR‐21 Contributes to Differential Macrophage Activation in Acute Kidney Injury in Aged Mice
Author(s) -
Pushpakumar Sathnur,
Kundu Sourav,
Givvimani Srikanth,
Sen Utpal
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.807.9
Subject(s) - acute kidney injury , macrophage , differential (mechanical device) , deregulation , medicine , kidney , cancer research , chemistry , physics , biochemistry , economics , macroeconomics , thermodynamics , in vitro
Age‐dependent renal changes increase the risk for acute kidney injury (AKI). The recruitment and activation of macrophages (M) is a prominent feature in this pathology wherein, distinct subsets of macrophages contribute to inflammation (M1) and tissue remodeling (M2). Recent studies suggest that microRNAs (miRs) play a significant role in AKI and functional recovery. The miRs are small non‐coding RNA's which inhibit mRNA transcripts or block protein translation thus affecting the microenvironment a vital factor in the differentiation of macrophages to M1 and M2 phenotype. In this study, we determined whether deregulation of miR‐21 contributes to macrophage polarization in renal ischemia reperfusion injury in aged mice. Young (12‐14 wks) and aged (72‐75 wks) wild type mice underwent bilateral renal ischemia for 25 minutes followed by 7 days reperfusion. Plasma creatinine and kidney injury molecule‐1 measurement revealed severe renal dysfunction in aged mice vs. young. The level of miR‐21 was increased in aged mice. Renal mononuclear cell preparation and staining with F4/80 and CD40/CD206 (M1, M2 respectively) revealed increased expression of CD40 in aged kidney. In addition, cytokine profiling showed increased mRNA and protein expression for TNFα, IL‐6 and decreased IL‐10 and Arg1 compared to young mice. Transfection of RAW264.7 cells (early vs. late passage) with miR‐21 mimic and lipopolysaccharide increased the levels of iNOS and TNFα suggesting pro‐inflammatory M1 response in late passage cells, whereas miR‐21 inhibitor diminished their expression. Our data suggests that following acute kidney injury in aged mice, dynamic changes in miR‐21 contributes to macrophage polarization leading to severe renal injury.