Regrowth of the rat biliary tree after 70% partial hepatectomy is coupled to increased secretin-induced ductal secretion

LeSage, Gene; Glaser, Shannon; Gubba, Siddeswar; Robertson, W.; Phinizy, Jo Lynne; Lasater, John; Rodgers, Rebecca; Alpini, Gianfranco

doi:10.1016/s0016-5085(96)70027-6

Cited by 133 publications

(293 citation statements)

References 13 publications

Supporting

Mentioning

279

Contrasting

Unclassified

Order By: Relevance

“…2,[5][6][7][8][9][10][11] For example, secretin enhances ductal secretory activity by interaction with specific receptors on cholangiocytes, 12 resulting in an increase in intracellular adenosine 3Ј,5Ј-monophosphate (cAMP) levels. [5][6][7]9,13,14 Increased cAMP levels induce the opening of Cl Ϫ channels and activation of the Cl Ϫ /HCO 3 Ϫ exchanger activity, which results in the secretin-induced bicarbonate-rich choleresis in vivo. [5][6][7]10,11,15 We have demonstrated that intrahepatic cholangiocytes are morphologically and functionally heterogeneous.…”

mentioning

confidence: 99%

“…6,11,18 However, cholangiocytes markedly proliferate in response to specific pathological stimuli/toxins. 2,6,10,11,[18][19][20][21][22][23] Cholangiocyte proliferation is closely associated with in-creased DNA synthesis, which leads to increased ductal hyperplasia. 2,6,10,11 Different patterns of cholangiocyte proliferation exist.…”

mentioning

confidence: 99%

“…2,6,10,11,[18][19][20][21][22][23] Cholangiocyte proliferation is closely associated with in-creased DNA synthesis, which leads to increased ductal hyperplasia. 2,6,10,11 Different patterns of cholangiocyte proliferation exist. Type I (typical) ductal hyperplasia is confined to the portal tract and is observed in rats after 70% partial hepatectomy, bile duct ligation (BDL), combined BDL/furan treatment, or ␣-naphthylisothiocyanate feeding.…”

mentioning

confidence: 99%

“…Type I (typical) ductal hyperplasia is confined to the portal tract and is observed in rats after 70% partial hepatectomy, bile duct ligation (BDL), combined BDL/furan treatment, or ␣-naphthylisothiocyanate feeding. [5][6][7]10,11,22,23 In this type of ductal hyperplasia, cholangiocytes maintain phenotypes of normal cholangiocyte lineage. 6,7,11 Type II (atypical) ductal hyperplasia can be noticed in prolonged liver diseases such as primary biliary cirrhosis 2,19,20 and is characterized by a poorly defined network of biliary conduits extending from the portal tract into the liver parenchyma.…”

mentioning

confidence: 99%

“…[5][6][7]10,11,22,23 In this type of ductal hyperplasia, cholangiocytes maintain phenotypes of normal cholangiocyte lineage. 6,7,11 Type II (atypical) ductal hyperplasia can be noticed in prolonged liver diseases such as primary biliary cirrhosis 2,19,20 and is characterized by a poorly defined network of biliary conduits extending from the portal tract into the liver parenchyma. Type III or ''oval'' cell hyperplasia is seen in the early phases of experimentally induced carcinogenesis in rat liver 2,22 and is characterized by disorganized proliferation of tubular structures consisting of ''oval'' cells into the liver parenchyma.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Acute Carbon Tetrachloride Feeding Selectively Damages Large, But Not Small, Cholangiocytes From Normal Rat Liver

et al. 1999

View full text Add to dashboard Cite

The aim of this study was to develop a model of selective duct damage restricted to hormone-responsive segments corresponding to the ducts damaged in primary biliary cirrhosis (PBC). Carbon tetrachloride (CCl 4 ) was fed by gavage to rats, and 2, 7, 14, and 28 days later, small and large cholangiocytes were isolated. Apoptosis was determined in situ by morphology and in purified cholangiocytes by assessment of nuclear fragmentation by 4,6-diamidino-2-phenylindole (DAPI) staining. Cholangiocyte proliferation was evaluated in situ by morphometry of liver sections stained for cytokeratin-19 (CK-19) and by proliferating cellular nuclear antigen (PCNA) staining in liver sections and in purified cholangiocytes by PCNA gene expression.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Acute Carbon Tetrachloride Feeding Selectively Damages Large, But Not Small, Cholangiocytes From Normal Rat Liver

et al. 1999

View full text Add to dashboard Cite

show abstract

Signaling pathways in biliary epithelial cells

Leite¹,

Guerra²,

Andrade³

et al. 2015

Signaling Pathways in Liver Diseases

View full text Add to dashboard Cite

Knockout of secretin receptor reduces large cholangiocyte hyperplasia in mice with extrahepatic cholestasis induced by bile duct ligation

et al. 2010

View full text Add to dashboard Cite

During bile duct ligation (BDL), the growth of large cholangiocytes is regulated by the cyclic adenosine monophosphate (cAMP)/extracellular signal-regulated kinase 1/2 (ERK1/ 2) pathway and is closely associated with increased secretin receptor (SR) expression. Although it has been suggested that SR modulates cholangiocyte growth, direct evidence for secretin-dependent proliferation is lacking. SR wild-type (WT) (SR) mice underwent sham surgery or BDL for 3 or 7 days. We evaluated SR expression, cholangiocyte proliferation, and apoptosis in liver sections and proliferating cell nuclear antigen (PCNA) protein expression and ERK1/2 phosphorylation in purified large cholangiocytes from WT and SR 2/2 BDL mice. Normal WT mice were treated with secretin (2.5 nmoles/kg/day by way of osmotic minipumps for 1 week), and biliary mass was evaluated. Small and large cholangiocytes were used to evaluate the in vitro effect of secretin (100 nM) on proliferation, protein kinase A (PKA) activity, and ERK1/2 phosphorylation. SR expression was also stably knocked down by short hairpin RNA, and basal and secretin-stimulated cAMP levels (a functional index of biliary growth) and proliferation were determined. SR was expressed by large cholangiocytes. Knockout of SR significantly decreased large cholangiocyte growth induced by BDL, which was associated with enhanced apoptosis. PCNA expression and ERK1/2 phosphorylation were decreased in large cholangiocytes from SR 2/2 BDL compared with WT BDL mice. In vivo administration of secretin to normal WT mice increased ductal mass. In vitro, secretin increased proliferation, PKA activity, and ERK1/2 phosphorylation of large cholangiocytes that was blocked by PKA and mitogen-activated protein kinase kinase inhibitors. Stable knockdown of SR expression reduced basal cholangiocyte proliferation. SR is an important trophic regulator sustaining biliary growth. Conclusion: The current study provides strong support for the potential use of secretin as a therapy for ductopenic liver diseases. (HEPATO-LOGY 2010;52:204-214)

show abstract

Regrowth of the rat biliary tree after 70% partial hepatectomy is coupled to increased secretin-induced ductal secretion

Abstract: After partial hepatectomy, the increase in secretin-induced ductal bile secretion observed during bile duct renewal results from proliferation of remaining cholangiocytes.

Cited by 133 publications

References 13 publications

Acute Carbon Tetrachloride Feeding Selectively Damages Large, But Not Small, Cholangiocytes From Normal Rat Liver

Acute Carbon Tetrachloride Feeding Selectively Damages Large, But Not Small, Cholangiocytes From Normal Rat Liver

Signaling pathways in biliary epithelial cells

Knockout of secretin receptor reduces large cholangiocyte hyperplasia in mice with extrahepatic cholestasis induced by bile duct ligation

Contact Info

Product

Resources

About