{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:54:27Z","timestamp":1790103267930,"version":"4.0.1"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1492,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>Liver fibrogenesis is a process tightly controlled by endogenous anti- and pro-fibrogenic factors. Interferon gamma (IFN\u03b3) is a potent antifibrogenic cytokine<\/jats:bold>\n                      <jats:bold>in vitro<\/jats:bold>\n                      <jats:bold>and might therefore represent a powerful therapeutic entity. However, its poor pharmacokinetics and adverse effects, due to the presence of IFN\u03b3 receptors on nearly all cells, prevented its clinical application so far. We hypothesized that delivery of IFN\u03b3 specifically to the disease-inducing cells and concurrently avoiding its binding to nontarget cells might increase therapeutic efficacy and avoid side effects. We conjugated IFN\u03b3 to a cyclic peptide recognizing the platelet-derived growth factor beta receptor (PDGF\u03b2R) which is strongly up-regulated on activated hepatic stellate cells (HSC), the key effector cells responsible for hepatic fibrogenesis. The IFN\u03b3 conjugates were analyzed<\/jats:bold>\n                      <jats:bold>in vitro<\/jats:bold>\n                      <jats:bold>for PDGF\u03b2R-specific binding and biological effects and<\/jats:bold>\n                      <jats:bold>in vivo<\/jats:bold>\n                      <jats:bold>in acute (early) and chronic (progressive and established) carbon-tetrachloride-induced liver fibrosis in mice. The targeted-IFN\u03b3 construct showed PDGF\u03b2R-specific binding to fibroblasts and HSC and inhibited their activation<\/jats:bold>\n                      <jats:bold>in vitro<\/jats:bold>\n                      .\n                      <jats:bold>In vivo<\/jats:bold>\n                      ,\n                      <jats:bold>the targeted-IFN\u03b3 construct attenuated local HSC activation in an acute liver injury model. In the established liver fibrosis model, it not only strongly inhibited fibrogenesis but also induced fibrolysis. In contrast, nontargeted IFN\u03b3 was ineffective in both models. Moreover, in contrast to unmodified IFN\u03b3, our engineered targeted-IFN\u03b3 did not induce IFN\u03b3-related side effects such as systemic inflammation, hyperthermia, elevated plasma triglyceride levels, and neurotropic effects.<\/jats:bold>\n                      <jats:bold>Conclusion:<\/jats:bold>\n                      <jats:bold>This study presents a novel HSC-targeted engineered-IFN\u03b3, which in contrast to systemic IFN\u03b3, blocked liver fibrogenesis and is devoid of side effects, by specifically acting on the key pathogenic cells within the liver. (Hepatology 2011;)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.24395","type":"journal-article","created":{"date-parts":[[2011,4,29]],"date-time":"2011-04-29T13:30:51Z","timestamp":1304083851000},"page":"586-596","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":86,"title":["Novel engineered targeted interferon-gamma blocks hepatic fibrogenesis in 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