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MicroRNA‐21 Antagonism Attenuates Inflammation and Endothelial‐Mesenchymal Transition in Aged Kidney Ischemia Reperfusion Injury
Author(s) -
Pushpakumar Sathnur,
Weber Gregory,
Majumder Suravi,
Sen Utpal
Publication year - 2018
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.2018.32.1_supplement.849.11
Subject(s) - inflammation , kidney , acute kidney injury , medicine , kidney disease , ischemia , population , endocrinology , immunology , pathology , environmental health
Ischemia‐reperfusion (IR) is one of the most common causes of acute kidney injury (AKI) in the aging population. MicroRNAs (miRs) are endogenous non‐coding RNA which have the ability to target the expression of multiple genes involved in the inflammatory and repair processes, thus influencing the course of disease. Although elevation of miR‐21 following renal IR has been observed in several studies involving young animals including humans, its role in the aged kidney remains unknown. The purpose of this study was to determine whether miR‐21 contributes directly to persistent inflammation in the aged kidney following IR injury and whether its inhibition attenuates inflammation to promote repair. Because profibrotic cues originating from inflammatory cells are known to favor endothelial‐mesenchymal transition (endoMT) by activation of myofibroblasts, we also investigated whether miR‐21 inhibition reduces endoMT. Wild type (WT, C57BL/6J) mice aged 12–14 wk and 75–78 wk were used in this study. After treatment without or with Locked Nucleic Acid Anti‐miR‐21 (20 mg/kg b.w.), mice underwent bilateral renal ischemia (27 min.) followed by reperfusion for 7 days. Aged mice exhibited severe renal IR injury and anti‐miR‐21 treatment improved glomerular filtration rate, renal blood flow and decreased renal resistive index. Anti‐miR‐21 treated mice demonstrated predominance of M2 macrophages associated with increased expression of arginase‐1 and IL‐4 and reduction of inflammatory cytokines. Further, anti‐miR‐21 reduced TGF‐β, matrix metalloproteinase‐9 and collagen expression in the aged kidney. Double labeling for endothelial marker, Tie2, and fibroblast markers, FSP‐1/α‐SMA showed significant reduction in their coexpression suggesting reduction in endoMT. Our findings suggest that miR‐21 inhibition reduces macrophage mediated inflammation and endoMT to promote reparative process following IR injury in the aged kidney. Support or Funding Information AHA grant to SP: 15SDG25840013NIH grant to US: DK104653 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .