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Hepatic stellate cells maintain liver homeostasis through paracrine neurotrophin-3 signaling that induces hepatocyte proliferation.
Trinh, Vincent Quoc-Huy; Lee, Ting-Fang; Lemoinne, Sara; Ray, Kevin C; Ybanez, Maria D; Tsuchida, Takuma; Carter, James K; Agudo, Judith; Brown, Brian D; Akat, Kemal M; Friedman, Scott L; Lee, Youngmin A.
Afiliación
  • Trinh VQ; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Lee TF; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Lemoinne S; Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Ray KC; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Ybanez MD; Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Tsuchida T; Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Carter JK; Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Agudo J; Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Brown BD; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Akat KM; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Friedman SL; Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Lee YA; Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sci Signal ; 16(787): eadf6696, 2023 05 30.
Article en En | MEDLINE | ID: mdl-37253090
Organ size is maintained by the controlled proliferation of distinct cell populations. In the mouse liver, hepatocytes in the midlobular zone that are positive for cyclin D1 (CCND1) repopulate the parenchyma at a constant rate to preserve liver mass. Here, we investigated how hepatocyte proliferation is supported by hepatic stellate cells (HSCs), pericytes that are in close proximity to hepatocytes. We used T cells to ablate nearly all HSCs in the murine liver, enabling the unbiased characterization of HSC functions. In the normal liver, complete loss of HSCs persisted for up to 10 weeks and caused a gradual reduction in liver mass and in the number of CCND1+ hepatocytes. We identified neurotrophin-3 (Ntf-3) as an HSC-produced factor that induced the proliferation of midlobular hepatocytes through the activation of tropomyosin receptor kinase B (TrkB). Treating HSC-depleted mice with Ntf-3 restored CCND1+ hepatocytes in the midlobular region and increased liver mass. These findings establish that HSCs form the mitogenic niche for midlobular hepatocytes and identify Ntf-3 as a hepatocyte growth factor.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neurotrofina 3 / Células Estrelladas Hepáticas / Hígado Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neurotrofina 3 / Células Estrelladas Hepáticas / Hígado Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos