ABSTRACT
Alcoholic liver disease (ALD) may be attributed to multiple hits driving several alterations. The aim of this work was to determine whether nucleoredoxin (NXN) interacts with flightless-I (FLII)/actin complex and how this ternary complex is altered during ALD progression induced by different ALD models. ALD was recapitulated in C57BL/6J female mice by the well-known ALD Lieber-DeCarli model, and by an in vitro human co-culture system overexpressing NXN. The effects of ethanol and low doses of lipopolysaccharides (LPS) and diethylnitrosamine (DEN) were also evaluated in vivo as a first approach of an ALD multi-hit protocol. We demonstrated that NXN interacts with FLII/actin complex. This complex was differentially altered in ALD in vivo and in vitro, and NXN overexpression partially reverted this alteration. We also showed that ethanol, LPS and DEN synergistically induced liver structural disarrangement, steatosis and inflammatory infiltration accompanied by increased levels of proliferation (Ki67), ethanol metabolism (CYP2E1), hepatocarcinogenesis (GSTP1) and LPS-inducible (MYD88 and TLR4) markers. In summary, we provide evidence showing that NXN/FLII/actin complex is involved in ALD progression and that NXN might be involved in the regulation of FLII/actin-dependent cellular functions. Moreover, we present a promising first approach of a multi-hit protocol to better recapitulate ALD pathogenesis.
Subject(s)
Fatty Liver/metabolism , Fatty Liver/pathology , Liver Diseases, Alcoholic/metabolism , Liver Diseases, Alcoholic/pathology , Microfilament Proteins/metabolism , Oxidoreductases/metabolism , Animals , Body Weight/drug effects , Cell Proliferation/drug effects , Cytochrome P-450 CYP2E1/metabolism , Diethylnitrosamine/pharmacology , Ethanol , Female , Lipopolysaccharides/pharmacology , Liver/metabolism , Liver/pathology , Mice , Mice, Inbred C57BLABSTRACT
This data contains information related to the research article entitled "Osteopontin splice variants and polymorphisms in Cancer Progression and Prognosis" [1]. Here, we describe an in silico analysis of transcription factors that could have altered binding to their DNA target sequence as a result of SNPs in the osteopontin gene promoter. We concentrated on SNPs associated with cancer risk and development. The analysis was performed with PROMO v3.0.2 software which incorporates TRANSFACT v6.4 of. We also present a figure depicting the putative transcription factor binding according to genotype.
