{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:44:34Z","timestamp":1788410674120,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T00:00:00Z","timestamp":1540252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-n\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY16H190002"],"award-info":[{"award-number":["LY16H190002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Liver biopsy is the current reliable way of evaluating liver fibrosis. However, no specific sera biomarker could be applied in clinical diagnosis. As the pivotal role of osteopontin (OPN) reported in numerous liver diseases, thrombin\u2010cleaved OPN (Thr\u2010OPN) exposes an integrin\u2010binding motif that promoted biological functions. Herein, we investigated the potential of Thr\u2010OPN in liver fibrosis. Using patient samples, mouse models and hepatic stellate cells (HSCs), we analyzed the involvement of Thr\u2010OPN in liver fibrosis. The result showed that, first, Thr\u2010OPN level was significantly higher in patients with\u00a0liver cirrhosis than that in patients with\u00a0chronic hepatitis B and healthy controls. Thr\u2010OPN level was positively correlated with liver fibrosis degree in clinical samples. Then in mouse models, it showed a similar correlation between hepatic Thr\u2010OPN levels and liver fibrosis degree. Thr\u2010OPN peptides exacerbated liver fibrosis in OPN\u2010deficient mice, whereas the neutralization of Thr\u2010OPN alleviated liver fibrosis in wild\u2010type mice. Furthermore, when compared with full\u2010length OPN (FL\u2010OPN), Thr\u2010OPN exhibited a greater ability to promote HSC activation, proliferation, and migration via mitogen\u2010activated protein (MAP) kinase and nuclear factor (NF)\u2010\u03baB pathways. In conclusion, Thr\u2010OPN, not FL\u2010OPN, was critically involved in the exacerbation of liver fibrosis by \u03b19 and \u03b14 integrins via MAP kinase and NF\u2010\u03baB signaling pathway, thus representing a novel diagnostic biomarker and treatment target for liver cirrhosis.<\/jats:p>","DOI":"10.1002\/jcp.27571","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T09:21:18Z","timestamp":1540286478000},"page":"8988-8997","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Thrombin cleavage of osteopontin controls activation of hepatic stellate cells and is essential for liver fibrogenesis"],"prefix":"10.1002","volume":"234","author":[{"given":"Guangying","family":"Cui","sequence":"first","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First 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