{"doi":"10.1002/jcb.30398","title":"Tyrosine phosphorylation of YAP‐1 in biliary epithelial cells mediates posthepatectomy liver regeneration and is affected by serotonin","abstract":"Experimental data suggested activation of yes-associated protein (YAP-1) as a critical regulator of liver regeneration (LR). Serotonin (5-HT) promotes LR in rodent models and has been proposed to act via YAP-1. How 5-HT affects LR is incompletely understood. A possible mechanism how 5-HT affects human LR was explored. Sixty-one patients were included. Tissue samples prior and 2 h after induction of LR were collected. Circulating levels of 5-HT and osteopontin (OPN) were assessed. YAP-1, its phosphorylation states, cytokeratin 19 (CK-19) and OPN were assessed using immunofluorescence. A mouse model of biliary epithelial cells (BECs) specific deletion of YAP/TAZ was developed. YAP-1 increased as early as 2 h after induction of LR (p = 0.025) predominantly in BECs. BEC specific deletion of YAP/TAZ reduced LR after 70% partial hepatectomy in mice (Ki67%, p < 0.001). SSRI treatment, depleting intra-platelet 5-HT, abolished YAP-1 and OPN induction upon LR. Portal vein 5-HT levels correlated with intrahepatic YAP-1 expression upon LR (R = 0.703, p = 0.035). OPN colocalized with YAP-1 in BECs and its circulating levels increased in the liver vein 2 h after induction of LR (p = 0.017). In the context of LR tyrosine-phosphorylated YAP-1 significantly increased (p = 0.042). Stimulating BECs with 5-HT resulted in increased YAP-1 activation via tyrosine-phosphorylation and subsequently increased OPN expression. BECs YAP-1 appears to be critical for LR in mice and humans. Our evidence suggests that 5-HT, at least in part, exerts its pro-regenerative effects via YAP-1 tyrosine-phosphorylation in BECs and subsequent OPN-dependent paracrine immunomodulation.","journal":"Journal of Cellular Biochemistry","year":2023,"id":356582,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":669992,"name":"Laura Brunnthaler","orcid":null,"position":1,"is_corresponding":false},{"id":994456,"name":"Ryan Watkins","orcid":"0000-0002-7061-3238","position":2,"is_corresponding":false},{"id":1075663,"name":"David Pereyra","orcid":"0000-0001-6700-9163","position":3,"is_corresponding":false},{"id":562307,"name":"Judith Stift","orcid":"0000-0001-5334-9343","position":4,"is_corresponding":false},{"id":1105660,"name":"Michaela Finsterbusch","orcid":"0000-0001-9470-4313","position":5,"is_corresponding":false},{"id":1075664,"name":"Jonas Santol","orcid":"0000-0002-8097-9735","position":6,"is_corresponding":false},{"id":1075667,"name":"Thomas Gruenberger","orcid":"0000-0002-2671-0540","position":7,"is_corresponding":false},{"id":669044,"name":"Alice Assinger","orcid":"0000-0002-5670-5910","position":8,"is_corresponding":false},{"id":230197,"name":"Rory L. Smoot","orcid":"0000-0001-8543-661X","position":9,"is_corresponding":false},{"id":363545,"name":"Patrick Starlinger","orcid":"0000-0002-4666-5337","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T01:13:30.556819Z","pmid":"36946436","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}