Molecular and functional heterogeneity of cholangiocytes from rat liver after bile duct ligation

Gianfranco Alpini, Charles Ulrich, Stuart Roberts, John O. Phillips, Yoshiyuki Ueno, Prasad V. Podila, Oscar Colegio, Gene D. LeSage, Laurence J Miller, Nicholas F La Russo

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Cholangiocytes, the epithelial cells that line intrahepatic bile ducts, participate in bile secretion via basal and agonist-stimulated transport of solutes and water. On the basis of subtle structural differences between cholangiocytes lining small vs. large bile ducts, as well as known phenotypic variations among transporting epithelia in other organs, we demonstrated that cholangiocytes are functionally heterogeneous along the intrahepatic biliary tree of normal rats. In studies reported here, we confirm and extend the concept of functional heterogeneity of cholangiocytes by employing the bile duct-ligated (BDL) rat model of cholestasis associated with selective cholangiocyte proliferation. Using novel isolation and separatory techniques, we prepared subpopulations of pure small, medium, and large cholangiocytes from BDL rats and compared them with regard to gene expression and basal or agonist-responsive transport activities. Although transcripts for γ-glutamyl transpeptidase and cytokeratin 19, two cholangiocyte-specific proteins, and glyceraldehyde-3-phosphate dehydrogenase, a housekeeping gene, were in all three subpopulations, genes for several proteins involved in solute transport [Cl /HCO3 exchanger, cystic fibrosis transmembrane conductance regulator (CFTR), and secretin receptor] were expressed only in medium and large cholangiocytes. Consistent with these findings, secretin increased intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) and 36Cl- efflux rates in medium and large cholangiocytes but not in small cholangiocytes. Also, forskolin/8-(4-chlorophenylthio)-cAMP stimulated 36Cl- efflux rates only in medium and large cholangiocytes, consistent with selective functional expression of CFTR in these subpopulations. These results support the molecular and functional heterogeneity of cholangiocytes within the intrahepatic biliary ductal system and are consistent with the notion that hormone-regulated transport of solutes after BDL occurs principally in medium and large cholangiocytes in a fashion similar to that observed in normal rat liver.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume272
Issue number2 35-2
StatePublished - Feb 1997

Fingerprint

Bile Ducts
Ligation
Cystic Fibrosis Transmembrane Conductance Regulator
Liver
Biliary Tract
Chloride-Bicarbonate Antiporters
Keratin-19
Intrahepatic Bile Ducts
Glyceraldehyde-3-Phosphate Dehydrogenases
Secretin
gamma-Glutamyltransferase
Cholestasis
Essential Genes
Colforsin
Bile
Cyclic AMP
Proteins
Epithelium
Epithelial Cells
Hormones

Keywords

  • gene expression
  • second messenger system
  • transport biliary epithelia

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Molecular and functional heterogeneity of cholangiocytes from rat liver after bile duct ligation. / Alpini, Gianfranco; Ulrich, Charles; Roberts, Stuart; Phillips, John O.; Ueno, Yoshiyuki; Podila, Prasad V.; Colegio, Oscar; LeSage, Gene D.; Miller, Laurence J; La Russo, Nicholas F.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 272, No. 2 35-2, 02.1997.

Research output: Contribution to journalArticle

Alpini, Gianfranco ; Ulrich, Charles ; Roberts, Stuart ; Phillips, John O. ; Ueno, Yoshiyuki ; Podila, Prasad V. ; Colegio, Oscar ; LeSage, Gene D. ; Miller, Laurence J ; La Russo, Nicholas F. / Molecular and functional heterogeneity of cholangiocytes from rat liver after bile duct ligation. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 1997 ; Vol. 272, No. 2 35-2.
@article{b0a130a393964336859bcb958522bd4c,
title = "Molecular and functional heterogeneity of cholangiocytes from rat liver after bile duct ligation",
abstract = "Cholangiocytes, the epithelial cells that line intrahepatic bile ducts, participate in bile secretion via basal and agonist-stimulated transport of solutes and water. On the basis of subtle structural differences between cholangiocytes lining small vs. large bile ducts, as well as known phenotypic variations among transporting epithelia in other organs, we demonstrated that cholangiocytes are functionally heterogeneous along the intrahepatic biliary tree of normal rats. In studies reported here, we confirm and extend the concept of functional heterogeneity of cholangiocytes by employing the bile duct-ligated (BDL) rat model of cholestasis associated with selective cholangiocyte proliferation. Using novel isolation and separatory techniques, we prepared subpopulations of pure small, medium, and large cholangiocytes from BDL rats and compared them with regard to gene expression and basal or agonist-responsive transport activities. Although transcripts for γ-glutamyl transpeptidase and cytokeratin 19, two cholangiocyte-specific proteins, and glyceraldehyde-3-phosphate dehydrogenase, a housekeeping gene, were in all three subpopulations, genes for several proteins involved in solute transport [Cl /HCO3 exchanger, cystic fibrosis transmembrane conductance regulator (CFTR), and secretin receptor] were expressed only in medium and large cholangiocytes. Consistent with these findings, secretin increased intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) and 36Cl- efflux rates in medium and large cholangiocytes but not in small cholangiocytes. Also, forskolin/8-(4-chlorophenylthio)-cAMP stimulated 36Cl- efflux rates only in medium and large cholangiocytes, consistent with selective functional expression of CFTR in these subpopulations. These results support the molecular and functional heterogeneity of cholangiocytes within the intrahepatic biliary ductal system and are consistent with the notion that hormone-regulated transport of solutes after BDL occurs principally in medium and large cholangiocytes in a fashion similar to that observed in normal rat liver.",
keywords = "gene expression, second messenger system, transport biliary epithelia",
author = "Gianfranco Alpini and Charles Ulrich and Stuart Roberts and Phillips, {John O.} and Yoshiyuki Ueno and Podila, {Prasad V.} and Oscar Colegio and LeSage, {Gene D.} and Miller, {Laurence J} and {La Russo}, {Nicholas F}",
year = "1997",
month = "2",
language = "English (US)",
volume = "272",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "2 35-2",

}

TY - JOUR

T1 - Molecular and functional heterogeneity of cholangiocytes from rat liver after bile duct ligation

AU - Alpini, Gianfranco

AU - Ulrich, Charles

AU - Roberts, Stuart

AU - Phillips, John O.

AU - Ueno, Yoshiyuki

AU - Podila, Prasad V.

AU - Colegio, Oscar

AU - LeSage, Gene D.

AU - Miller, Laurence J

AU - La Russo, Nicholas F

PY - 1997/2

Y1 - 1997/2

N2 - Cholangiocytes, the epithelial cells that line intrahepatic bile ducts, participate in bile secretion via basal and agonist-stimulated transport of solutes and water. On the basis of subtle structural differences between cholangiocytes lining small vs. large bile ducts, as well as known phenotypic variations among transporting epithelia in other organs, we demonstrated that cholangiocytes are functionally heterogeneous along the intrahepatic biliary tree of normal rats. In studies reported here, we confirm and extend the concept of functional heterogeneity of cholangiocytes by employing the bile duct-ligated (BDL) rat model of cholestasis associated with selective cholangiocyte proliferation. Using novel isolation and separatory techniques, we prepared subpopulations of pure small, medium, and large cholangiocytes from BDL rats and compared them with regard to gene expression and basal or agonist-responsive transport activities. Although transcripts for γ-glutamyl transpeptidase and cytokeratin 19, two cholangiocyte-specific proteins, and glyceraldehyde-3-phosphate dehydrogenase, a housekeeping gene, were in all three subpopulations, genes for several proteins involved in solute transport [Cl /HCO3 exchanger, cystic fibrosis transmembrane conductance regulator (CFTR), and secretin receptor] were expressed only in medium and large cholangiocytes. Consistent with these findings, secretin increased intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) and 36Cl- efflux rates in medium and large cholangiocytes but not in small cholangiocytes. Also, forskolin/8-(4-chlorophenylthio)-cAMP stimulated 36Cl- efflux rates only in medium and large cholangiocytes, consistent with selective functional expression of CFTR in these subpopulations. These results support the molecular and functional heterogeneity of cholangiocytes within the intrahepatic biliary ductal system and are consistent with the notion that hormone-regulated transport of solutes after BDL occurs principally in medium and large cholangiocytes in a fashion similar to that observed in normal rat liver.

AB - Cholangiocytes, the epithelial cells that line intrahepatic bile ducts, participate in bile secretion via basal and agonist-stimulated transport of solutes and water. On the basis of subtle structural differences between cholangiocytes lining small vs. large bile ducts, as well as known phenotypic variations among transporting epithelia in other organs, we demonstrated that cholangiocytes are functionally heterogeneous along the intrahepatic biliary tree of normal rats. In studies reported here, we confirm and extend the concept of functional heterogeneity of cholangiocytes by employing the bile duct-ligated (BDL) rat model of cholestasis associated with selective cholangiocyte proliferation. Using novel isolation and separatory techniques, we prepared subpopulations of pure small, medium, and large cholangiocytes from BDL rats and compared them with regard to gene expression and basal or agonist-responsive transport activities. Although transcripts for γ-glutamyl transpeptidase and cytokeratin 19, two cholangiocyte-specific proteins, and glyceraldehyde-3-phosphate dehydrogenase, a housekeeping gene, were in all three subpopulations, genes for several proteins involved in solute transport [Cl /HCO3 exchanger, cystic fibrosis transmembrane conductance regulator (CFTR), and secretin receptor] were expressed only in medium and large cholangiocytes. Consistent with these findings, secretin increased intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) and 36Cl- efflux rates in medium and large cholangiocytes but not in small cholangiocytes. Also, forskolin/8-(4-chlorophenylthio)-cAMP stimulated 36Cl- efflux rates only in medium and large cholangiocytes, consistent with selective functional expression of CFTR in these subpopulations. These results support the molecular and functional heterogeneity of cholangiocytes within the intrahepatic biliary ductal system and are consistent with the notion that hormone-regulated transport of solutes after BDL occurs principally in medium and large cholangiocytes in a fashion similar to that observed in normal rat liver.

KW - gene expression

KW - second messenger system

KW - transport biliary epithelia

UR - http://www.scopus.com/inward/record.url?scp=0030900791&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030900791&partnerID=8YFLogxK

M3 - Article

C2 - 9124353

AN - SCOPUS:0030900791

VL - 272

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 2 35-2

ER -