EGF Activates Autocrine TGFα to Induce Prolonged EGF Receptor Signaling and Hepatocyte Proliferation

Background/Aims: EGF receptor is a main participant in the regulation of liver regeneration. In primary hepatocyte cultures, EGF or TGFα binding to EGF receptor activates Erk1/2 and PI3K pathways, induces cyclin D1 and thus initiates DNA synthesis. We have explored mechanisms by which prolonged EGF receptor activation induces hepatocyte proliferation. Methods: EGF receptor activation, as well as Erk1/2 and PI3K signaling were explored in EGF-stimulated primary hepatocyte cultures by Western blotting and immunocytochemistry. TGFα release to the medium was quantified by ELISA. Effects of a neutralizing antibody to TGFα on EGF receptor signaling and proliferation were explored. Results: Inhibitors of PI3K or Erk1/2 inhibited cyclin D1 expression and G1 progression when added 12 hours after EGF stimulation, whereas depletion of EGF from the medium at this time point did not. ELISA demonstrated that EGF induced TGFα release to the medium. Cyclin D1 induction and cellular proliferation were efficiently inhibited when a neutralizing antibody to TGFα was added to the medium. This also occurred when the antibody was added 12 hours after EGF stimulation. Conclusion: Sustained EGF receptor activity and signaling through both Erk1/2 and PI3K pathways were necessary for proliferation. This was achieved by EGF activation of autocrine TGFα

Understanding microplastic pollution in the Nordic marine environment – knowledge gaps and suggested approaches

This paper examines a number of specific, practical recommendations to advance knowledge and move towards evidence-based solutions to microplastic (MP) pollution in the Nordic marine environment. The paper approaches the subject of MPs holistically, emphasises the knowledge gaps and challenges in answering pressing questions, discusses the limitations that so far have prevented these questions from being solved, and suggests approaches for answering them. The Nordic context is chosen due to the global importance of its ecosystem that is threatened by MP pollution, exacerbated by climate change. The research questions discussed pick up knowledge gaps identified in attempts to answer the most pressing questions of our time regarding marine MP pollution and are applicable to some or all seas of the Nordic region, from the Baltic and North Seas in the south to the Arctic in the north. The research questions relate to sources, sinks and transport of MPs, and how food webs are potentially impacted in Nordic marine environments. In addition, we point out the relevance for stakeholders expected to use the emerging knowledge. Through this exercise, using concrete examples, we aim to invite discussions on how a concerted effort by the Nordic countries can bring MP research to a higher level of understanding needed to address the MP pollution problem in Nordic marine habitats.publishedVersio