Vol. 123, No. 1 (Supplement) 2018
Supplement abstract

The role of the secretin/secretin receptor axis in the modulation of liver fibrosis via changes in TGF-1β- mediated biliary senescence

PDF
  • Romina Mancinelli,
  • Antonio Franchitto,
  • Gianfranco Alpini,
  • Paolo Onori,
  • Luigi Pannarale,
  • Eugenio Gaudio
Romina Mancinelli
Sapienza University of Rome, Dipartimento scienze anatomiche, istologiche, medico legali e dell’apparato locomotore, Roma, Italia
Antonio Franchitto
Sapienza Università di Roma, Dipartimento scienze anatomiche, istologiche, medico legali e dell’apparato locomotore, Roma, Italia
Gianfranco Alpini
Texas A&M Health Science Center, Department of Medicine and Medical Physiology, Temple, Texas, Italia
Paolo Onori
Sapienza Università di Roma, Dipartimento scienze anatomiche, istologiche, medico legali e dell’apparato locomotore, Roma, Italia
Luigi Pannarale
Sapienza Università di Roma, Dipartimento scienze anatomiche, istologiche, medico legali e dell’apparato locomotore, Roma, Italia
Eugenio Gaudio
Sapienza Università di Roma, Dipartimento scienze anatomiche, istologiche, medico legali e dell’apparato locomotore, Roma, Italia
DOI: https://doi.org/10.13128/ijae-11438

Published 2018-12-30

Keywords

  • Biliary epithelium,
  • cholangiocytes,
  • fibrosis,
  • secretin

How to Cite

Mancinelli, R., Franchitto, A., Alpini, G., Onori, P., Pannarale, L., & Gaudio, E. (2018). The role of the secretin/secretin receptor axis in the modulation of liver fibrosis via changes in TGF-1β- mediated biliary senescence. Italian Journal of Anatomy and Embryology, 123(1), 131. https://doi.org/10.13128/ijae-11438
Copyright Notice

Abstract

The biliary epithelium and its cells, cholangiocytes, are the target in several human chol- angiopathies including primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), which are diseases characterized by extensive fibrosis (1). Proliferating cholangiocytes display neuroendocrine characteristics and secrete and respond to several neuropeptides and gastrointestinal hormones that modulate cholangiocyte responses to injury via autocrine/par- acrine mechanisms (2). Secretin (Sct) exerts its effects through secretin receptor (SR), which is expressed in the liver by large cholangiocytes. Enhanced biliary proliferation during cholestasis is associated with increased SR expression on cholangiocytes and increased cAMP dependent secretin-stimulated ductal secretion (3). Our aim was to define the role of Sct-regulated cellular senescence and demonstrated that liver fibrosis is significantly reduced in Sct-/-, SR-/- and Sct- /-/SR-/- BDL mice compared to BDL wild-type (WT) mice. The reduction in hepatic fibrosis in Sct-/-, SR-/- and Sct-/-/SR-/- BDL mice was accompanied by reduced TGF-β1 levels in serum and cholangiocyte supernatant as well as decreased expression of markers of cellular senes- cence in cholangiocytes in contrast to increased expression of cellular senescence in hepatic stellate cells (HSCs) compared to BDL WT mice. Sct directly stimulated the senescence of chol- angiocytes and regulated by a paracrine mechanism the senescence of HSCs and liver fibrosis via modulation of TGF-β1 biliary secretion. Targeting senescent cholangiocytes may represent a novel therapeutic approach for ameliorating hepatic fibrosis during cholestatic liver injury.

PDF

Metrics

Metrics Loading ...