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  • We also observed a significantly higher SLC A

    2022-08-09

    We also observed a significantly higher SLC10A1 gene expression and NTCP protein level among metastatic individuals vs. donor livers. Na+/taurocholate co-transporting polypeptide (NTCP), which is expressed on the basolateral membrane of hepatocytes and is primarily responsible for the uptake of bile acids from the sinusoids, has been recently recognized as the main HBV entry receptor [25]. Interestingly, it was demonstrated that SLC10A1 expression and function was suppressed by IL-6 in HepaRG SCH772984 and primary hepatocytes [23,26]. However, other factors are known to be involved in NTCP transcriptional regulation, i.e. bile salts, sex hormones and glucocorticoids [27]. Hence, other clinical factors, SCH772984 beyond the presence of tumor, might also be responsible for the observed differences between the analyzed subsets of liver tissues. The present study also demonstrates that the correlation between gene expression and protein abundance of the studied transporters was different, and the values of correlation coefficient were all below 0.8, for ABCB11/BSEP, SLC22A1/OCT1 and SLC22A3/OCT3 between metastatic and donor livers. These observations, and lack of correlation between mRNA and protein content for most of the analyzed drug transporters suggest that measurement of gene expression at mRNA level may not be a proper tool to determine changes in transporter function in human liver. The findings also suggest that hepatic transporter processing is regulated by other mechanisms beyond transcription. Involvement of microRNA was evidenced for P-gp abundance regulation, which was significantly different in the studied donor and nontumoral metastatic livers [28,29]. Apart from the quantitative differences in transporter levels observed between the donor and metastatic livers, greater inter-individual variability in all studied transporters’ protein abundance in subjects with metastatic colon cancer was observed, and it was evidenced by a higher covariance coefficient in the case of all the analyzed targets (Fig. 1, Fig. 2, Fig. 3, Fig. 4 and Supplementary Table 3). As a consequence, using donor livers as a reference would probably make a study more sensitive and enable detection of even minor differences in case-control studies.
    Acknowledgements The study was funded a grant by the National Science Centre, Cracow, Poland UMO-2015/18/M/NZ7/000410.
    Introduction Cyanobacteria comprise an ancient, large, and morphologically diverse group of gram-negative bacteria. They were the first organisms to evolve oxygenic photosynthesis on Earth, thereby creating the oxic atmosphere (Adams and Duggan, 1999; Rippka et al., 1979). With their relatively fast growth rate and ease of genetic manipulation, cyanobacteria are promising organisms for bioengineering and for creating cell factories that use CO2 to produce various useful chemicals, such biofuels and bioplastics (Angermayr et al., 2015; Oliver et al., 2016). However, these valuable photoautotrophs are also involved in processes with negative consequences. For instance, they sometimes form toxic blooms that negatively influence ecosystems and consequently human health (Huisman et al., 2018). The freshwater cyanobacterium Anabaena sp. PCC 7120 (hereafter Anabaena sp.) belongs to Section IV (filamentous heterocystous cyanobacteria) according to the classification of (Rippka et al., 1979). This prokaryotic model organism is used for studying nitrogen fixation and cell differentiation. Anabaena sp. forms non-branching filaments or trichomes composed of several hundred cells (Fig. 1) (Rippka et al., 1979). When grown in the presence of a combined nitrogen source, the trichomes consist mostly of vegetative cells, but when combined nitrogen is lacking, Anabaena sp. develops heterocysts that arise in the filaments in a semi-regular pattern, every 10th to 20th cell. Heterocysts specialize in N2 fixation and transport N-assimilation products to the neighboring vegetative cells. In turn, they obtain sugars produced by photosynthesis from the vegetative cells. Signaling molecules are transported along the filament to ensure the pattern of heterocysts and a coordinated behavior of this multicellular organism (Herrero et al., 2016). Molecule exchange occurs via cell–cell joining multiprotein complexes, called septal junctions, in the nanopores of the septal cell wall (Flores et al., 2018a, 2016; Weiss et al., 2018).