{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:13:05Z","timestamp":1790806385862,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011002","name":"National Natural Science Foundation of China-Yunnan Joint Fund","doi-asserted-by":"publisher","award":["81600504"],"award-info":[{"award-number":["81600504"]}],"id":[{"id":"10.13039\/501100011002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011002","name":"National Natural Science Foundation of China-Yunnan Joint Fund","doi-asserted-by":"publisher","award":["81700573"],"award-info":[{"award-number":["81700573"]}],"id":[{"id":"10.13039\/501100011002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>T\u2010cell immunoglobulin domain and mucin domain\u20104 (TIM\u20104) is selectively expressed on antigen\u2010presenting cells (APCs) and modulates various immune responses. However, the role of TIM\u20104 expressed by Kupffer cells (KCs) in liver fibrosis remains unclear. The present study aimed to explore whether and how TIM\u20104 expressed by KCs is involved in liver fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Mice chronic liver fibrosis models were established and divided into the olive\u2010induced control group, CCL4\u2010induced control group, olive\u2010induced TIM\u20104 interference group and CCL4\u2010induced TIM\u20104 interference group. Different techniques were used to monitor the fibrotic effects of TIM\u20104, including histopathological assays, Western blotting, ELISA and transmission electron microscopy. Additionally, mice liver transplant models were established to determine the fibrotic effects of TIM\u20104 on fibrosis after liver transplantation (LT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that the induction of liver fibrosis by\u00a0CCL4\u00a0was associated with TIM\u20104 expression in KCs. TIM\u20104 interference essentially contributed to liver fibrosis resolution. KCs from the TIM\u20104 interference group had decreased levels of pro\u2010fibrotic markers, reduced TGF\u2010\u03b21 secretion and inhibited hepatic stellate cell (HSC) differentiation into myofibroblast\u2010like cells. In addition, we used GdCl3 to verify that KCs are the primary source of TGF\u2010\u03b21 during fibrosis progression. Moreover, KCs from CCL4\u2010induced mice showed increased ROS production, mitophagy activation and TGF\u2010\u03b21 secretion. However, TIM\u20104 interference in the KCs inhibited Akt1\u2010mediated ROS production, resulting in the suppression of PINK1, Parkin and LC3\u2010II\/I activation and the reduction of TGF\u2010\u03b21 secretion during liver fibrosis. Additionally, TIM\u20104 interference potentially attenuated development of fibrosis after LT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings revealed the underlying mechanisms of TIM\u20104 interference in KCs to mitigate liver fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cpr.12731","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T05:41:40Z","timestamp":1574401300000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["TIM\u20104 interference in Kupffer cells against CCL4\u2010induced liver fibrosis by mediating Akt1\/Mitophagy signalling 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