Putative MicroRNA Regulatory Networks in Hepatic Stellate Cells Underlying Chronic Ethanol‐Mediated Impairment of Liver Regeneration after Partial Hepatectomy

microRNAs (miRNAs) are a class of small, non‐coding RNAs ~22 nucleotides in length that are involved in post‐transcriptional regulation of a wide variety of processes critical for normal cell function, such as development, cell differentiation, cell proliferation, and cell death. There remains, however, a comparative lack of knowledge on the precise role and function of miRNAs in the context of alcoholic liver disease. In this study, we sought to characterize global miRNA expression patterns in the rat liver for both control and ethanol‐fed animals before and after 70% partial hepatectomy (PHx). Chronic ethanol consumption using the Lieber‐DeCarli diet leads to a maladaptive response across multiple organ systems, and is sufficient by itself to alter normal miRNA expression dynamics in the liver. This adaptation to ethanol consumption has also been shown to alter miRNA expression in response to PHx when compared with control animals. Additionally, the regenerative capacity of the liver in response to injury is significantly decreased by chronic ethanol consumption. Previous research has identified several miRNAs that may be key regulators of liver regeneration, such as miR‐21, whose role in liver regeneration and liver disease has been well‐studied by our lab and others. By using the NanoString nCounter expression system, we obtained an un‐biased view of changes in miRNA expression. Our results show that the differentially expressed miRNAs exhibit complex expression dynamics during liver regeneration, and that many of these miRNAs appear to be strongly correlated with each other, suggesting the possibility of co‐regulatory networks. This is further supported by our results showing that alteration of the expression of a single miRNA, in this case inhibition of miR‐21, is capable of affecting the expression of multiple other miRNAs in both correlated and anti‐correlated fashions. Functional analysis of these dysregulated miRNAs suggests potential mechanisms involved in hepatic stellate cell activity, which was further supported by gene set enrichment analysis using previously published data involving stellate cell‐specific miRNAs. In conclusion, we have identified a network of miRNAs whose differential expression may regulate liver regeneration via alteration of hepatic stellate cell function. Support or Funding Information Research was supported by the following NIH grants from NIAAA: R01 AA018873, U01EB023224, F31 AA024969‐01, and T32 AA007463. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .