Premium
miR‐21 inhibition overcomes ethanol suppression of rat liver regeneration
Author(s) -
Juskeviciute Egle,
Dippold Rachael P.,
Swarup Aditi,
Hoek Jan B.
Publication year - 2013
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.27.1_supplement.257.3
Subject(s) - liver regeneration , proliferating cell nuclear antigen , regeneration (biology) , cell cycle , microrna , biology , hepatectomy , e2f , cell growth , downregulation and upregulation , apoptosis , cancer research , andrology , microbiology and biotechnology , endocrinology , medicine , biochemistry , gene , surgery , resection
miR‐21 has been identified as a pro‐proliferative miRNA. It is overexpressed in many types of tumors. miR‐21 also increases its expression during liver regeneration following partial hepatectomy (PHx) in the rat in apparent agreement with this pro‐proliferative role. However, chronic ethanol treated animals which have impaired liver regeneration show even stronger up‐regulation of miR‐21 expression than their corresponding pair‐fed calorie‐matched controls or chow fed animals (Dippold et al., 2012). To investigate the role of miR‐21 in liver regeneration, we treated rats with a locked oligonucleotide antisense to miR‐21 (AM21). Injection of AM21 72 h prior to PHx followed by a second injection immediately after the surgery suppressed expression of miR‐21 by >;95% in the regenerating rat liver. Inhibition of miR‐21 resulted in up‐regulation of expression of such validated miR‐21 targets as RhoB, E2f1, Il6ra, Nfib and Tgfbr2. AM21 treatment did not have any significant effect on cell cycle progression markers, such as cyclins D, E, A, PCNA either at the mRNA or the protein level in chow fed animals. Remarkably, however, AM21 treatment promoted cell cycle progression and allowed recovery of DNA synthesis 24h after PHx in chronically ethanol treated animals. Thus, miR‐21 is not required for normal progression of liver regeneration after PHx in the rat. Supported by AA008714 , AA018873 , AA007463 , and AA017261.