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Considering the crucial role of transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) in the emergence of these diseases, the present study tested the hypothesis that LGALS3BP regulates the TGF\u2010\u03b21 signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The expression levels of\n                      <jats:italic>LGALS3BP<\/jats:italic>\n                      and\n                      <jats:italic>TGFB1<\/jats:italic>\n                      were analyzed in patients with metabolic dysfunction\u2010associated steatohepatitis (MASH) and HCC. Multiple omics techniques, such as RNA\u2010sequencing, transposase\u2010accessible chromatin\u2010sequencing assay, and liquid chromatography\u2010tandem mass spectrometry proteomics, were used to identify the regulatory mechanisms for the LGALS3BP\u2010TGF\u2010\u03b21 axis. The effects of altered TGF\u2010\u03b21 signaling by LGALS3BP were investigated in conditional\n                      <jats:italic>LGALS3BP<\/jats:italic>\n                      \u2010knockin and\n                      <jats:italic>LGALS3BP<\/jats:italic>\n                      \u2010knockout mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In patients with MASH and HCC, the levels of\n                      <jats:italic>LGALS3BP<\/jats:italic>\n                      and\n                      <jats:italic>TGFB1<\/jats:italic>\n                      exhibited positive correlations. Stimulation of LGALS3BP by the inflammatory cytokine interferon \u03b1 in HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of TGFB1. Aggravated fibrosis was observed in the livers of hepatocyte\u2010specific\n                      <jats:italic>LGALS3BP<\/jats:italic>\n                      \u2010knockin mice, with increased TGFB1 levels. LGALS3BP directly bound to and assembled integrin \u03b1V, an integral mediator required for releasing active TGF\u2010\u03b21 from extracellular latent complex with the rearranged F\u2010actin cytoskeleton. The released TGF\u2010\u03b21 activated JunB transcription factor, which in turn promoted the TGF\u2010\u03b21 positive feedback loop.\n                      <jats:italic>LGALS3BP<\/jats:italic>\n                      deletion in the hepatocytes downregulated TGF\u2010\u03b21 signaling and CCl\n                      <jats:sub>4<\/jats:sub>\n                      induced fibrosis. Moreover,\n                      <jats:italic>LGALS3BP<\/jats:italic>\n                      depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF\u2010\u03b21.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF\u2010\u03b21 signaling pathway, making it a promising therapeutic target in TGF\u2010\u03b21\u2010related diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cac2.12600","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:09:00Z","timestamp":1722211740000},"page":"1106-1129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Galectin 3\u2010binding protein (LGALS3BP) depletion attenuates hepatic fibrosis by reducing transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) availability and inhibits hepatocarcinogenesis"],"prefix":"10.34133","volume":"44","author":[{"given":"Dae\u2010Hwan","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Division of Hematology and Oncology Chonnam National University Medical School  Hwasun South Korea"},{"name":"Department of Internal Medicine Division of Hematology and Oncology Chonnam National University Hwasun Hospital  Hwasun South Korea"},{"name":"Combinatorial Tumor Immunotherapy MRC Center Chonnam National University Medical School  Hwasun South Korea"},{"name":"National Immunotherapy Innovation Center  Hwasun South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjeong","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Hematology and Oncology Chonnam National University Medical School  Hwasun South 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