Literature DB >> 27115285

The secretin/secretin receptor axis modulates liver fibrosis through changes in transforming growth factor-β1 biliary secretion in mice.

Nan Wu1, Fanyin Meng2,3,4,1, Pietro Invernizzi5,6, Francesca Bernuzzi5,6, Julie Venter1, Holly Standeford2, Paolo Onori7, Marco Marzioni8, Domenico Alvaro9, Antonio Franchitto7,10, Eugenio Gaudio7, Shannon Glaser2,3,1, Gianfranco Alpini2,3,1.   

Abstract

UNLABELLED: The secretin/secretin receptor (SR) axis is up-regulated by proliferating cholangiocytes during cholestasis. Secretin stimulates biliary proliferation by down-regulation of let-7a and subsequent up-regulation of the growth-promoting factor, nerve growth factor (NGF). It is not known whether the secretin/SR axis plays a role in subepithelial fibrosis observed during cholestasis. Our aim was to determine the role of the secretin/SR axis in activation of biliary fibrosis in animal models and human primary sclerosing cholangitis (PSC). Studies were performed in wild-type (WT) mice with bile duct ligation (BDL), BDL SR(-/-) mice, or Mdr2(-/-) mouse models of cholestatic liver injury. In selected studies, the SR antagonist (Sec 5-27) was used to block the secretin/SR axis. Biliary proliferation and fibrosis were evaluated as well as secretion of secretin (by cholangiocytes and S cells), expression of markers of fibrosis, transforming growth factor-β1 (TGF-β1), transforming growth factor-β1 receptor (TGF-β1R), let-7a, and downstream expression of NGF. Correlative studies were performed in human control and PSC liver tissue biopsies, serum, and bile. SR antagonist reduced biliary proliferation and hepatic fibrosis in BDL WT and Mdr2(-/-) mice. There was decreased expression of let-7a in BDL and Mdr2(-/-) cholangiocytes that was associated with increased NGF expression. Inhibition of let-7a accelerated liver fibrosis was attributed to cholestasis. There was increased expression of TGF-β1 and TGF-β1R. Significantly higher expression of secretin, SR, and TGF-β1 was observed in PSC patient liver samples compared to healthy controls. In addition, there was higher expression of fibrosis genes and remarkably decreased expression of let-7a and increased expression of NGF compared to the control.
CONCLUSION: The secretin/SR axis plays a key role in regulating the biliary contribution to cholestasis-induced hepatic fibrosis. (Hepatology 2016;64:865-879).
© 2016 by the American Association for the Study of Liver Diseases.

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Year:  2016        PMID： 27115285      PMCID： PMC4992423          DOI： 10.1002/hep.28622

Source DB:  PubMed          Journal:  Hepatology        ISSN： 0270-9139            Impact factor:   17.425


  40 in total

1.  Histological and ultrastructural examination of the intrahepatic biliary tree in primary sclerosing cholangitis.

Authors:  Y Nakanuma; N Hirai; N Kono; G Ohta
Journal:  Liver       Date:  1986-12

2.  Secretin stimulates cyclic AMP formation in the rat brain.

Authors:  R T Fremeau; L Y Korman; T W Moody
Journal:  J Neurochem       Date:  1986-06       Impact factor: 5.372

3.  Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis.

Authors:  J M de Vree; E Jacquemin; E Sturm; D Cresteil; P J Bosma; J Aten; J F Deleuze; M Desrochers; M Burdelski; O Bernard; R P Oude Elferink; M Hadchouel
Journal:  Proc Natl Acad Sci U S A       Date:  1998-01-06       Impact factor: 11.205

4.  Functional properties of murine macrophages promoted by nerve growth factor.

Authors:  Y Susaki; S Shimizu; K Katakura; N Watanabe; K Kawamoto; M Matsumoto; M Tsudzuki; T Furusaka; Y Kitamura; H Matsuda
Journal:  Blood       Date:  1996-12-15       Impact factor: 22.113

5.  Immunohistochemical detection of chloride/bicarbonate anion exchangers in human liver.

Authors:  E Martínez-Ansó; J E Castillo; J Díez; J F Medina; J Prieto
Journal:  Hepatology       Date:  1994-06       Impact factor: 17.425

6.  Intracoronary secretin increases cardiac perfusion and function in anaesthetized pigs through pathways involving β-adrenoceptors and nitric oxide.

Authors:  Elena Grossini; Claudio Molinari; Vera Morsanuto; David A S G Mary; Giovanni Vacca
Journal:  Exp Physiol       Date:  2012-12-13       Impact factor: 2.969

7.  Transforming growth factor-beta (TGF-beta) protein levels are not elevated in the blood or bile of patients with primary sclerosing cholangitis: a pilot study.

Authors:  J K Watt; K Hawkins; M Zhang; J Lipschitz; G Sandha; Y Gong; J Uhanova; G Y Minuk
Journal:  Dig Dis Sci       Date:  2004-01       Impact factor: 3.199

8.  Upregulation of secretin receptor gene expression in rat cholangiocytes after bile duct ligation.

Authors:  G Alpini; C D Ulrich; J O Phillips; L D Pham; L J Miller; N F LaRusso
Journal:  Am J Physiol       Date:  1994-05

9.  Transforming growth factor-β1-mediated renal fibrosis is dependent on the regulation of transforming growth factor receptor 1 expression by let-7b.

Authors:  Bo Wang; Jay C Jha; Shinji Hagiwara; Aaron D McClelland; Karin Jandeleit-Dahm; Merlin C Thomas; Mark E Cooper; Phillip Kantharidis
Journal:  Kidney Int       Date:  2013-10-02       Impact factor: 10.612

Review 10.  Secretin as a neuropeptide.

Authors:  Samuel S M Ng; W H Yung; Billy K C Chow
Journal:  Mol Neurobiol       Date:  2002-08       Impact factor: 5.590
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  49 in total

1.  Prolonged darkness reduces liver fibrosis in a mouse model of primary sclerosing cholangitis by miR-200b down-regulation.

Authors:  Nan Wu; Fanyin Meng; Tianhao Zhou; Yuyan Han; Lindsey Kennedy; Julie Venter; Heather Francis; Sharon DeMorrow; Paolo Onori; Pietro Invernizzi; Francesca Bernuzzi; Romina Mancinelli; Eugenio Gaudio; Antonio Franchitto; Shannon Glaser; Gianfranco Alpini
Journal:  FASEB J       Date:  2017-06-20       Impact factor: 5.191

2.  The TGFβ1 Receptor Antagonist GW788388 Reduces JNK Activation and Protects Against Acetaminophen Hepatotoxicity in Mice.

Authors:  Matthew McMillin; Stephanie Grant; Gabriel Frampton; Anca D Petrescu; Elaina Williams; Brandi Jefferson; Sharon DeMorrow
Journal:  Toxicol Sci       Date:  2019-05-01       Impact factor: 4.849

3.  Knockout of the Tachykinin Receptor 1 in the Mdr2-/- (Abcb4-/-) Mouse Model of Primary Sclerosing Cholangitis Reduces Biliary Damage and Liver Fibrosis.

Authors:  Ludovica Ceci; Heather Francis; Tianhao Zhou; Thao Giang; Zhihong Yang; Fanyin Meng; Nan Wu; Lindsey Kennedy; Konstantina Kyritsi; Vik Meadows; Chaodong Wu; Suthat Liangpunsakul; Antonio Franchitto; Amelia Sybenga; Burcin Ekser; Romina Mancinelli; Paolo Onori; Eugenio Gaudio; Shannon Glaser; Gianfranco Alpini
Journal:  Am J Pathol       Date:  2020-07-23       Impact factor: 4.307

4.  Modulation of the Tryptophan Hydroxylase 1/Monoamine Oxidase-A/5-Hydroxytryptamine/5-Hydroxytryptamine Receptor 2A/2B/2C Axis Regulates Biliary Proliferation and Liver Fibrosis During Cholestasis.

Authors:  Konstantina Kyritsi; Lixian Chen; April O'Brien; Heather Francis; Travis W Hein; Julie Venter; Nan Wu; Ludovica Ceci; Tianhao Zhou; David Zawieja; Anatoliy A Gashev; Fanyin Meng; Pietro Invernizzi; Luca Fabris; Chaodong Wu; Nicholas J Skill; Romil Saxena; Suthat Liangpunsakul; Gianfranco Alpini; Shannon S Glaser
Journal:  Hepatology       Date:  2019-10-18       Impact factor: 17.425

5.  Knockout of microRNA-21 attenuates alcoholic hepatitis through the VHL/NF-κB signaling pathway in hepatic stellate cells.

Authors:  Nan Wu; Kelly McDaniel; Tianhao Zhou; Sugeily Ramos-Lorenzo; Chaodong Wu; Li Huang; Demeng Chen; Tami Annable; Heather Francis; Shannon Glaser; Gianfranco Alpini; Fanyin Meng
Journal:  Am J Physiol Gastrointest Liver Physiol       Date:  2018-05-31       Impact factor: 4.052

6.  Knockdown of Hepatic Gonadotropin-Releasing Hormone by Vivo-Morpholino Decreases Liver Fibrosis in Multidrug Resistance Gene 2 Knockout Mice by Down-Regulation of miR-200b.

Authors:  Konstantina Kyritsi; Fanyin Meng; Tianhao Zhou; Nan Wu; Julie Venter; Heather Francis; Lindsey Kennedy; Paolo Onori; Antonio Franchitto; Francesca Bernuzzi; Pietro Invernizzi; Kelly McDaniel; Romina Mancinelli; Domenico Alvaro; Eugenio Gaudio; Gianfranco Alpini; Shannon Glaser
Journal:  Am J Pathol       Date:  2017-05-12       Impact factor: 4.307

7.  Pinealectomy or light exposure exacerbates biliary damage and liver fibrosis in cholestatic rats through decreased melatonin synthesis.

Authors:  Lixian Chen; Tianhao Zhou; Nan Wu; April O'Brien; Julie Venter; Ludovica Ceci; Konstantina Kyritsi; Paolo Onori; Eugenio Gaudio; Amelia Sybenga; Linglin Xie; Chaodong Wu; Luca Fabris; Pietro Invernizzi; David Zawieja; Suthat Liangpunsakul; Fanyin Meng; Heather Francis; Gianfranco Alpini; Qiaobing Huang; Shannon Glaser
Journal:  Biochim Biophys Acta Mol Basis Dis       Date:  2019-03-16       Impact factor: 5.187

Review 8.  Regulators of Cholangiocyte Proliferation.

Authors:  Chad Hall; Keisaku Sato; Nan Wu; Tianhao Zhou; Konstantina Kyritsi; Fanyin Meng; Shannon Glaser; Gianfranco Alpini
Journal:  Gene Expr       Date:  2016-07-12

9.  The Secretin/Secretin Receptor Axis Modulates Ductular Reaction and Liver Fibrosis through Changes in Transforming Growth Factor-β1-Mediated Biliary Senescence.

Authors:  Nan Wu; Fanyin Meng; Tianhao Zhou; Julie Venter; Thao K Giang; Konstantina Kyritsi; Chaodong Wu; Domenico Alvaro; Paolo Onori; Romina Mancinelli; Eugenio Gaudio; Heather Francis; Gianfranco Alpini; Shannon Glaser; Antonio Franchitto
Journal:  Am J Pathol       Date:  2018-07-21       Impact factor: 4.307

Review 10.  Ductular Reaction in Liver Diseases: Pathological Mechanisms and Translational Significances.

Authors:  Keisaku Sato; Marco Marzioni; Fanyin Meng; Heather Francis; Shannon Glaser; Gianfranco Alpini
Journal:  Hepatology       Date:  2018-12-27       Impact factor: 17.425
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