Nucleoredoxin interaction with flightless-I/actin complex is differentially altered in alcoholic liver disease.
Brisa Rodope Alarcón-SánchezDafne Guerrero-EscaleraSandra Rosas-MadrigalDiana Ivette Aparicio-BautistaKarina Reyes-GordilloM Raj LakshmanArturo Ortiz-FernándezHéctor QuezadaÓscar Medina-ContrerasSaúl Villa-TreviñoJulio Isael Pérez-CarreónJaime Arellanes-RobledoPublished in: Basic & clinical pharmacology & toxicology (2020)
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.
Keyphrases
- inflammatory response
- toll like receptor
- randomized controlled trial
- endothelial cells
- immune response
- cell migration
- type diabetes
- squamous cell carcinoma
- transcription factor
- gold nanoparticles
- anti inflammatory
- liver injury
- skeletal muscle
- high glucose
- diabetic rats
- radiation therapy
- neoadjuvant chemotherapy
- lymph node
- high fat diet induced