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This study aimed to determine whether RS504393, a selective CCR2 antagonist, can inhibit the progression of AE by blocking the CCL2\u2013CCR2 axis and modulating its downstream pathogenic mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, bioinformatics analysis of the GSE124362 dataset was combined with molecular docking simulations. Liver tissues from patients with AE and from\n                      <jats:italic>Echinococcus multilocularis<\/jats:italic>\n                      -infected mice were examined through histopathological and immunohistochemical staining methods. Pathological alterations and parasitic load were assessed by Western blot and quantitative real-time PCR (RT-PCR). An in vitro co-culture model involving\n                      <jats:italic>Echinococcus multilocularis<\/jats:italic>\n                      protoscolex-stimulated endothelial progenitor cells (EPCs), JS1 hepatic stellate cells (JS1) and RAW264.7 macrophages was established to evaluate angiogenesis, fibrogenic activity and macrophage polarization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Integrated bioinformatics and molecular docking analyses revealed CCL2\u2013CCR2 overexpression and high-affinity binding during AE progression. Treatment with RS504393 significantly attenuated hepatic fibrosis, suppressed phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) pathway activation and reduced M2 macrophage polarization in central lesion tissue of\n                      <jats:italic>E. multilocularis<\/jats:italic>\n                      -infected mice . In vitro, RS504393 inhibited angiogenesis driven by EPCs, induced apoptosis in JS1 cells, and redirected macrophage polarization from the M2 towards a more anti-parasitic phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CCR2 blockade with RS504393 attenuates AE progression by inhibiting PI3K-AKT signaling, suppressing angiogenesis and inducing stellate cell apoptosis, collectively reducing hepatic fibrosis and parasitic burden. Our findings provide a mechanistic rationale for repurposing CCR2 antagonists as a novel host-directed therapeutic strategy for echinococcosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-026-07306-3","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:37:48Z","timestamp":1777484268000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Blockade of the CCL2\u2013CCR2 axis attenuates fibrosis and parasite load in vesicular echinococcosis by inhibiting the PI3K-AKT pathway that regulates angiogenesis and hepatic stellate cell apoptosis"],"prefix":"10.1186","volume":"19","author":[{"given":"Bin","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menggen","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwei","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"7306_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-020-04103-4","volume":"13","author":"NM Bakhtiar","year":"2020","unstructured":"Bakhtiar NM, Spotin A, Mahami-Oskouei M, Ahmadpour E, Rostami A.\u00a0Recent advances on innate immune pathways related to host-parasite cross-talk in cystic and alveolar echinococcosis. 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