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Dissecting the role of the hepatocyte Epidermal Growth Factor Receptor (EGFR) pathway in the cellular interactome within the liver fibrotic niche

20th national competition for scientific and technical research

Intercellular Dialogue and Interactome: Pathological Implications

Senior Researcher : Isabel Fabregat Romero

Research Centre or Institution : Instituto de Investigación Biomédica de Bellvitge (IDIBELL). Barcelona.


Liver fibrosis is the consequence of chronic liver injury in the presence of an inflammatory component. Although the main executors of this activation are known, the mechanisms that lead to the inflammatory process that mediates the production of profibrotic factors are not well characterized. The Epidermal Growth Factor Receptor (EGFR) signaling in hepatocytes is essential for the regenerative process of the liver; however, its potential role in regulating the fibrotic niche is not yet clear. Our group generated and validated a mouse model that expresses an inactive truncated form of the EGFR in hepatocytes (ΔEGFR mice). This project aimed to analyze the role of the hepatocyte EGFR pathway in the fibrotic niche cell interactome in WT and ΔEGFR mice subjected to two models of experimental liver fibrosis (hepatocyte or biliary). During the first half of the project, results of the in vivo models have indicated that the hepatocyte-specific EGFR activity regulates the interaction between parenchymal and non-parenchymal liver cells, promoting the proinflammatory response, activated due to the liver damage, and, indeed, contributing to the pathogenesis of the disease. In vitro studies reveal that hepatocytes may directly regulate the macrophage phenotype by inducing the secretion of specific factors, whose expression depends on the activation of the EGFR pathway. Transcriptomic and proteomic studies, currently being performed, will allow to elucidate the specific molecular mechanisms regulated by EGFR that are responsible for the observed changes in the hepatocyte secretory phenotype.


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Magazine Articles 1
Communications at national conferences 1
Communications at international conferences 1


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