{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:56:33Z","timestamp":1787032593866,"version":"build-2736575974"},"posted":{"date-parts":[[2026,2,25]]},"group-title":"Cell Biology","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R35GM149261"],"award-info":[{"award-number":["R35GM149261"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Liver sinusoidal endothelial cells (LSECs) play essential roles in liver regeneration after injury, but the underlying mechanisms remain incompletely defined. Here we report that leukemia inhibitory factor (LIF), which is rapidly induced after liver injury, acts as a key regulator of LSECs-driven liver regeneration through interaction with LSECs-enriched LIF receptor (LIFR). LIF directly stimulates LSECs proliferation and induces hepatocyte growth factor (HGF) release in a dose-dependent manner via LIFR signaling in LSECs, thereby indirectly promoting hepatocyte proliferation. Systemic LIF neutralization or endothelial cells (ECs)-specific\n                  <jats:italic>Lifr<\/jats:italic>\n                  loss impairs liver regeneration, whereas low-titer AAV-mediated LIF expression increases vascular density, elevates circulating HGF, and improves early liver recovery after partial hepatectomy (PHx) in mice. Together, these findings establish LIF-LIFR as a previously unrecognized endothelial axis to promote hepatocyte proliferation and suggest potential therapeutic strategies to enhance liver repair in patients.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"order\">\n                    <jats:list-item>\n                      <jats:p>LIF is upregulated after liver injury and LIF neutralization impairs liver recovery.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        LIFR displays the highest expression in ECs; endothelial-specific\n                        <jats:italic>Lifr<\/jats:italic>\n                        deletion delays liver regeneration after injury.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>LIF mediates a positive feedback loop including LSECs proliferation as well as HGF release via LIFR pathway.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>LIF overexpression increases liver-to-body weight ratio in a dose-dependent manner and accelerates liver regeneration at early stage.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Abstract Graphic<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"707802v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.24.707802","type":"posted-content","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T12:40:13Z","timestamp":1772109613000},"source":"Crossref","is-referenced-by-count":1,"title":["The LIF-LIFR Axis Promotes Liver Regeneration via Modulation of Angiogenesis and HGF Release from LSECs"],"prefix":"10.64898","author":[{"given":"Wenjing","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pathology, University of California, San Diego, La Jolla, CA 92093,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Diemer","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Diego, La Jolla, CA 92093,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Diego, La Jolla, CA 92093,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna Chaitanya","family":"Ginne","sequence":"additional","affiliation":[{"name":"Department of Physics & Astronomy, Michigan State University, East Lansing, MI, USA \u2013 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumar R.N.","family":"Naresh","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Diego, La Jolla, CA 92093,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Diego, La Jolla, CA 92093,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilima","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Diego, La Jolla, CA 92093,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Piermarocchi","sequence":"additional","affiliation":[{"name":"Department of Physics & Astronomy, Michigan State University, East Lansing, MI, USA \u2013 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Napoleone","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Diego, La Jolla, CA 92093,"},{"name":"Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026030120400740000_2026.02.24.707802v1.1","doi-asserted-by":"crossref","unstructured":"X. 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