{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Minutti CM"],"funding":["European Union","Medical Research Council","Wellcome Trust"],"pagination":["645-654.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6436929"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["50(3)"],"pubmed_abstract":["The epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functioned by releasing bioactive transforming growth factor beta (TGF-β) from latent complexes via integrin-α<sub>V</sub> activation. Using acute injury models in two different tissues, we found that by inducing TGF-β activation on mesenchymal stromal cells (pericytes), Amphiregulin induced their differentiation into myofibroblasts, thereby selectively contributing to the restoration of vascular barrier function within injured tissue. Furthermore, we identified macrophages as a critical source of Amphiregulin, revealing a direct effector mechanism by which these cells contribute to tissue restoration after acute injury. Combined, these observations expose a so far under-appreciated mechanism of how cells of the immune system selectively control the differentiation of tissue progenitor cells during tissue repair and inflammation."],"journal":["Immunity"],"pubmed_title":["A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation."],"pmcid":["PMC6436929"],"funding_grant_id":["103749/Z/14/Z","103749","095898/Z/11/Z&apos;","106122/A/14/Z","MR/M011755/1","095898/Z/11/Z","MC_PC_18048","095898/Z/11/Z'","CIG-631413"],"pubmed_authors":["Blair N","Modak RV","Dobie R","Minutti CM","Smyth DJ","Li F","Henderson NC","Giampazolias E","Kopf M","Maizels RM","Griggs DW","Dorward DA","Muir A","Macdonald F","Kendall TJ","Husovsky C","Zaiss DM"],"additional_accession":[]},"is_claimable":false,"name":"A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation.","description":"The epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functioned by releasing bioactive transforming growth factor beta (TGF-β) from latent complexes via integrin-α<sub>V</sub> activation. Using acute injury models in two different tissues, we found that by inducing TGF-β activation on mesenchymal stromal cells (pericytes), Amphiregulin induced their differentiation into myofibroblasts, thereby selectively contributing to the restoration of vascular barrier function within injured tissue. Furthermore, we identified macrophages as a critical source of Amphiregulin, revealing a direct effector mechanism by which these cells contribute to tissue restoration after acute injury. Combined, these observations expose a so far under-appreciated mechanism of how cells of the immune system selectively control the differentiation of tissue progenitor cells during tissue repair and inflammation.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Mar","modification":"2026-05-07T03:25:36.925Z","creation":"2026-04-07T22:34:15.917Z"},"accession":"S-EPMC6436929","cross_references":{"pubmed":["30770250"],"doi":["10.1016/j.immuni.2019.01.008"]}}