{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T23:20:38Z","timestamp":1780960838477,"version":"3.54.1"},"reference-count":103,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20334760"],"award-info":[{"award-number":["20334760"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H04161"],"award-info":[{"award-number":["17H04161"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24659367"],"award-info":[{"award-number":["24659367"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A huge effort has been devoted to developing drugs targeting integrins over 30 years, because of the primary roles of integrins in the cell-matrix milieu. Five \u03b1v-containing integrins, in the 24 family members, have been a central target of fibrosis. Currently, a small molecule against \u03b1v\u03b21 is undergoing a clinical trial for NASH-associated fibrosis as a rare agent aiming at fibrogenesis. Latent TGF\u03b2 activation, a distinct talent of \u03b1v-integrins, has been intriguing as a therapeutic target. None of the \u03b1v-integrin inhibitors, however, has been in the clinical market. \u03b1v-integrins commonly recognize an Arg-Gly-Asp (RGD) sequence, and thus the pharmacophore of inhibitors for the 5-integrins is based on the same RGD structure. The RGD preference of the integrins, at the same time, dilutes ligand specificity, as the 5-integrins share ligands containing RGD sequence such as fibronectin. With the inherent little specificity in both drugs and targets, \u201cdisease specificity\u201d has become less important for the inhibitors than blocking as many \u03b1v-integrins. In fact, an almighty inhibitor for \u03b1v-integrins, pan-\u03b1v, was in a clinical trial. On the contrary, approved integrin inhibitors are all specific to target integrins, which are expressed in a cell-type specific manner: \u03b1IIb\u03b23 on platelets, \u03b14\u03b21, \u03b14\u03b27 and \u03b1L\u03b22 on leukocytes. Herein, \u201cdisease specific\u201d integrins would serve as attractive targets. \u03b18\u03b21 and \u03b111\u03b21 are selectively expressed in hepatic stellate cells (HSCs) and distinctively induced upon culture activation. The exceptional specificity to activated HSCs reflects a rather \u201cpathology specific\u201d nature of these new integrins. The monoclonal antibodies against \u03b18\u03b21 and \u03b111\u03b21 in preclinical examinations may illuminate the road to the first medical agents.<\/jats:p>","DOI":"10.3390\/ijms222312794","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:28Z","timestamp":1638314548000},"page":"12794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["New Therapeutic Targets for Hepatic Fibrosis in the Integrin Family, \u03b18\u03b21 and \u03b111\u03b21, Induced Specifically on Activated Stellate Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Yasuyuki","family":"Yokosaki","sequence":"first","affiliation":[{"name":"Integrin-Matrix Biomedical Science, Translational Research Center, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihisa","family":"Nishimichi","sequence":"additional","affiliation":[{"name":"Integrin-Matrix Biomedical Science, Translational Research Center, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/hep.29466","article-title":"Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease","volume":"67","author":"Estes","year":"2018","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/liv.13682","article-title":"Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening","volume":"38","author":"Marcellin","year":"2018","journal-title":"Liver Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/hep.31236","article-title":"Lysyl Oxidase (LOX) Family Members: Rationale and Their Potential as Therapeutic Targets for Liver Fibrosis","volume":"72","author":"Chen","year":"2020","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1111\/liv.13706","article-title":"Improvement of hepatic fibrosis and patient-reported outcomes in non-alcoholic steatohepatitis treated with selonsertib","volume":"38","author":"Younossi","year":"2018","journal-title":"Liver Int."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Slack, R.J., Macdonald, S.J.F., Roper, J.A., Jenkins, R.G., and Hatley, R.J.D. 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