Tight junctional permeability of the resting and carbachol stimulated exocrine rabbit pancreas

Kuijpers, Gemma A.J.; Nooy, I.G.P. Van; Vossen, Mirjam; Stadhouders, A. M.; Uyen, A. Van; Pont, J.J.H.H.M. de; Bonting, S.L.

doi:10.1007/bf00953994

Cited by 13 publications

(8 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, vasopressin, epinephrine, and angiotensin increase TJ permeability in perfused rodent liver . A similar effect is observed in pancreas in response to cholinergic stimulation . Two general mechanisms for regulation of TJ permeability have been proposed.…”

mentioning

confidence: 88%

Liver kinase B1 regulates hepatocellular tight junction distribution and function in vivo

et al. 2016

View full text Add to dashboard Cite

Liver Kinase B1 (LKB1) and its downstream effector AMP-activated protein kinase (AMPK) play critical roles in polarity establishment by regulating membrane trafficking and energy metabolism. In collagen sandwich-cultured hepatocytes, loss of LKB1 or AMPK impaired apical ABCB11 (Bsep) trafficking, and bile canalicular formation. In the present study, we used liver-specific (Albumin-Cre) LKB1 knockout mice (LKB1−/−) to investigate the role of LKB1 in the maintenance of functional tight junction (TJ) in vivo. Transmission electron microscopy (TEM) revealed that hepatocyte apical membrane with microvilli substantially extended into the basolateral domain of LKB1 −/− livers. Immunofluorescence (IF) studies showed that loss of LKB1 leads to longer and wider canalicular structures correlating with mis-localization of the junctional protein, cingulin. To test junctional function, we used Intravital Microscopy (IVM) to quantify the transport kinetics of 6-carboxy-fluorescein diacetate (6-CFDA), which is processed in hepatocytes into its fluorescent derivative 6-carboxyfluorescein (6-CF) and secreted into the canaliculi. In LKB1 −/− mice, 6-CF largely remained in hepatocytes, canalicular secretion was greatly delayed and 6-CF appeared in the blood. To test whether 6-CF was transported through permeable TJ, we intravenously injected a low molecular weight (3kDa) dextran in combination with 6-CFDA. In wild type mice, 3kDa dextran remained in the vasculature whereas it rapidly appeared in the abnormal bile canaliculi in LKB1 −/− mice, confirming that junctional disruption resulted in paracellular exchange between the blood stream and the bile canaliculus. Conclusion LKB1 plays a critical role in regulating maintenance of TJ and paracellular permeability, which may explain how various drugs, chemicals, and metabolic states that inhibit the LKB1/AMPK pathway, result in cholestasis.

show abstract

mentioning

confidence: 88%

Liver kinase B1 regulates hepatocellular tight junction distribution and function in vivo

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The barrier function controls the paracellular passage of solutes, ions, and various molecules. The structure of tight junctions in pancreatic exocrine and duct epithelial cells is dynamic and can be disrupted by, for example, carbachol and ductal hypertension [22–24]. Disruption of tight junctions unseals the paracellular spaces of adjacent cells, leading to unlimited movement of solutes, etc., into and out of the paracellular spaces, so causing edema and diarrhea [21].…”

Section: Introductionmentioning

confidence: 99%

Adhesion molecules and pancreatitis

2018

View full text Add to dashboard Cite

Acute and chronic pancreatitises are gastrointestinal inflammatory diseases, the incidence of which is increasing worldwide. Most (~ 80%) acute pancreatitis (AP) patients have mild disease, and about 20% have severe disease, which causes multiple organ failure and has a high mortality rate. Chronic pancreatitis (CP) is characterized by chronic inflammation and destruction of normal pancreatic parenchyma, which leads to loss of exocrine and endocrine tissues. Patients with CP also have a higher incidence of pancreatic ductal adenocarcinoma. Although a number of factors are associated with the development and progression of AP and CP, the underlying mechanism is unclear. Adhesion molecules play important roles in cell migration, proliferation, and signal transduction, as well as in development and tissue repair. Loosening of cell-cell adhesion between pancreatic acinar cells and/or endothelial cells increases solute permeability, resulting in interstitial edema, which promotes inflammatory cell migration and disrupts tissue structure. Oxidative stress, which is one of the important pathogenesis of pancreatitis, leads to upregulation of adhesion molecules. Soluble adhesion molecules are reportedly involved in AP. In this review, we focus on the roles of tight junctions (occludin, tricellulin, claudin, junctional adhesion molecule, and zonula occludin), adherens junctions (E-cadherin and p120-, α-, and β-catenin), and other adhesion molecules (selectin and intercellular adhesion molecules) in the progression of AP and CP. Maintaining the normal function of adhesion molecules and preventing their abnormal activation maintain the structure of the pancreas and prevent the development of pancreatitis.

show abstract

“…Kuijpers et al 9 reported a slight decrease in the number of strands and the depth of TJ in carbacholstimulated acinar cells. We also observed a decrease in the area and number of strands in the 20-IH and SS groups.…”

Section: Discussionmentioning

confidence: 98%

“…7,9,11,12,16,19 Correlation between the number of strands and paracellular electrical resistance or solute reflux impedance was also investigated. 18 Physiological analysis 19 showed a decreased number of strands and a barrier defect in inflamed colonic mucosa in patients with ulcerative colitis.…”

Section: Discussionmentioning

confidence: 99%

“…The results of observations using the FF technique suggest that the structure of the TJ is flexible and varies according to the condition of paracellular permeability. [7][8][9][10][11][12][13] In this study, we created an experimental model of acute obstruction of the main pancreatic duct by either intraductal hypertension (IH) or by secretin stimulation Abstract: The tight junction of pancreatic exocrine cells is thought to regulate paracellular permeability, and is a possible reflux route of pancreatic juice into the blood flow. Morphological changes in the tight junction of canine pancreatic acinar cells following intraductal hypertension and secretin stimulation were morphometrically analyzed to obtain evidence of the control of the paracellular reflux.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The tight junction of pancreatic exocrine cells is a morphometrically dynamic structure altered by intraductal hypertension

Akao

Oya

Akiyama

et al. 2000

Journal of Gastroenterology

View full text Add to dashboard Cite

The tight junction of pancreatic exocrine cells is thought to regulate paracellular permeability, and is a possible reflux route of pancreatic juice into the blood flow. Morphological changes in the tight junction of canine pancreatic acinar cells following intraductal hypertension and secretin stimulation were morphometrically analyzed to obtain evidence of the control of the paracellular reflux. Pancreatic tissues obtained from 25 dogs after intraductal hypertension, 3 dogs after secretin stimulation, and 5 control dogs were studied. Intraductal pressure was either 20 cmH2O, 30 cmH2O, or 40 cmH2O. Freeze fracture replicas of these pancreatic tissues were observed by electron microscopy. Tight junctions were classified into six morphometric types. Reticular type, parallel type, and mixed type comprised the common types predominantly found in all groups, and three special types were found, infrequently, only after intraductal hypertension. The percentages of the common types were significantly different between the groups. The areas of the tight junctions, and other morphometric parameters, were significantly less after 20 cmH2O intraductal hypertension and secretin stimulation than in the controls. However, these findings after 30 cmH2O or 40 cmH2O intraductal hypertension did not differ from those in the controls. The areas of the three special types of tight junctions were larger than those of the common types. These results suggest that the tight junction of pancreatic exocrine cells is a morphologically dynamic structure that is altered by the extent of intraductal hypertension, and support the hypothesis that paracellular permeability is the mechanism of the reflux of pancreatic juice.

show abstract

Tight junctional permeability of the resting and carbachol stimulated exocrine rabbit pancreas

Cited by 13 publications

References 25 publications

Liver kinase B1 regulates hepatocellular tight junction distribution and function in vivo

Liver kinase B1 regulates hepatocellular tight junction distribution and function in vivo

Adhesion molecules and pancreatitis

The tight junction of pancreatic exocrine cells is a morphometrically dynamic structure altered by intraductal hypertension

Contact Info

Product

Resources

About