Galectin-3 regulates hepatic progenitor cell expansion during liver injury

Research output: Contribution to journalArticlepeer-review

Authors

  • Wei-Chen Hsieh
  • Alison C Mackinnon
  • Jonathan Jung
  • Luke Boulter
  • Neil C Henderson
  • Kenneth J. Simpson
  • Baukje Schotanus
  • Davina Wojtacha
  • Tom G Bird
  • Claire N Medine
  • David C Hay
  • Tariq Sethi
  • John P Iredale
  • Stuart J Forbes

Colleges, School and Institutes

Abstract

Objective Following chronic liver injury or when hepatocyte proliferation is impaired, ductular reactions containing hepatic progenitor cells (HPCs) appear in the periportal regions and can regenerate the liver parenchyma. HPCs exist in a niche composed of myofibroblasts, macrophages and laminin matrix. Galectin-3 (Gal-3) is a β-galactoside-binding lectin that binds to laminin and is expressed in injured liver in mice and humans.

Design We examined the role of Gal-3 in HPC activation. HPC activation was studied following dietary induced hepatocellular (choline-deficient ethionine-supplemented diet) and biliary (3,5-diethoxycarbonyl-1,4-dihydrocollidine supplemented diet) injury in wild type and Gal-3(−/−) mice.

Results HPC proliferation was significantly reduced in Gal-3(−/−) mice. Gal-3(−/−) mice failed to form a HPC niche, with reduced laminin formation. HPCs isolated from wild type mice secrete Gal-3 which enhanced adhesion and proliferation of HPCs on laminin in an undifferentiated form. These effects were attenuated in Gal3(−/−) HPCs and in wild type HPCs treated with the Gal-3 inhibitor lactose. Gal-3(−/−) HPCs in vitro showed increased hepatocyte function and prematurely upregulated both biliary and hepatocyte differentiation markers and regulated cell cycle genes leading to arrest in G0/G1.

Conclusions We conclude that Gal-3 is required for the undifferentiated expansion of HPCs in their niche in injured liver.

Details

Original languageEnglish
Pages (from-to)312-321
Number of pages10
JournalGut
Volume64
Issue number2
Publication statusPublished - 16 May 2014