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Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis.
Kennedy, Lindsey; Francis, Heather; Invernizzi, Pietro; Venter, Julie; Wu, Nan; Carbone, Marco; Gershwin, M Eric; Bernuzzi, Francesca; Franchitto, Antonio; Alvaro, Domenico; Marzioni, Marco; Onori, Paolo; Gaudio, Eugenio; Sybenga, Amelia; Fabris, Luca; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco.
Afiliação
  • Kennedy L; Research, Central Texas Veterans Health Care System, Temple, Texas, USA.
  • Francis H; Department of Medical Physiology, Texas A&M University, College of Medicine, Temple, Texas, USA.
  • Invernizzi P; Research, Central Texas Veterans Health Care System, Temple, Texas, USA.
  • Venter J; Department of Medical Physiology, Texas A&M University, College of Medicine, Temple, Texas, USA.
  • Wu N; Baylor Scott & White Health Digestive Disease Research Center, Baylor Scott and White Health, Temple, Texas, USA.
  • Carbone M; Humanitas Clinical and Research Center, Rozzano (MI), Italy.
  • Gershwin ME; Department of Medical Physiology, Texas A&M University, College of Medicine, Temple, Texas, USA.
  • Bernuzzi F; Department of Medical Physiology, Texas A&M University, College of Medicine, Temple, Texas, USA.
  • Franchitto A; Humanitas Clinical and Research Center, Rozzano (MI), Italy.
  • Alvaro D; Division of Rheumatology, Allergy, and Clinical Immunology, University of California-Davis, Davis, California, USA.
  • Marzioni M; Humanitas Clinical and Research Center, Rozzano (MI), Italy.
  • Onori P; Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy.
  • Gaudio E; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
  • Sybenga A; Clinic of Gastroenterology and Hepatology, Universita Politecnica delle Marche, Ancona, Italy.
  • Fabris L; Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
  • Meng F; Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
  • Glaser S; Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • Alpini G; Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy.
FASEB J ; 33(9): 10269-10279, 2019 09.
Article em En | MEDLINE | ID: mdl-31251081
Primary biliary cholangitis (PBC) primarily targets cholangiocytes and is characterized by liver fibrosis and biliary proliferation. Activation of the secretin (Sct)/secretin receptor (SR) axis, expressed only by cholangiocytes, increases biliary proliferation, liver fibrosis, and bicarbonate secretion. We evaluated the effectiveness of SR antagonist treatment for early-stage PBC. Male and female dominant-negative TGF-ß receptor II (dnTGF-ßRII) (model of PBC) and wild-type mice at 12 wk of age were treated with saline or the SR antagonist, Sec 5-27, for 1 wk. dnTGF-ßRII mice expressed features of early-stage PBC along with enhanced Sct/SR axis activation and Sct secretion. dnTGF-ßRII mice had increased biliary proliferation or senescence, inflammation, and liver fibrosis. In dnTGF-ßRII mice, there was increased microRNA-125b/TGF-ß1/TGF-ß receptor 1/VEGF-A signaling. Human early-stage PBC patients had an increase in hepatobiliary Sct and SR expression and serum Sct levels. Increased biliary Sct/SR signaling promotes biliary and hepatic damage during early-stage PBC.-Kennedy, L., Francis, H., Invernizzi, P., Venter, J., Wu, N., Carbone, M., Gershwin, M. E., Bernuzzi, F., Franchitto, A., Alvaro, D., Marzioni, M., Onori, P., Gaudio, E., Sybenga, A., Fabris, L., Meng, F., Glaser, S., Alpini, G. Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Biliares / Receptores dos Hormônios Gastrointestinais / Secretina / Receptores Acoplados a Proteínas G / Receptor do Fator de Crescimento Transformador beta Tipo II / Inflamação / Cirrose Hepática / Cirrose Hepática Biliar Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Biliares / Receptores dos Hormônios Gastrointestinais / Secretina / Receptores Acoplados a Proteínas G / Receptor do Fator de Crescimento Transformador beta Tipo II / Inflamação / Cirrose Hepática / Cirrose Hepática Biliar Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos