ArticleHepatology (Baltimore, Md.)2016
Liver kinase B1 regulates hepatocellular tight junction distribution and function in vivo.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
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- SEW2871 attenuates ANIT-induced hepatotoxicity by protecting liver barrier function via sphingosine 1-phosphate receptor-1-mediated AMPK signaling pathway.Cell biology and toxicology · 2021Article
- Intravital Microscopy for the Study of Hepatic Glucose Uptake.Current protocols · 2021Article
- Tight junctions and their regulation by non-coding RNAs.International journal of biological sciences · 2021Review
- Liver Zonation - Revisiting Old Questions With New Technologies.Frontiers in physiology · 2021Review
- Leptin Influence Cholelithiasis Formation by Regulating Bile Acid Metabolism.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2021Article
- Intermittent Starvation Extends the Functional Lifetime of Primary Human Hepatocyte Cultures.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Visualization of Hepatocellular Regeneration in Mice After Partial Hepatectomy.The Journal of surgical research · 2019Article
- From a common progenitor to distinct liver epithelial phenotypes.Current opinion in cell biology · 2018Review
- The role of microtubules in the regulation of epithelial junctions.Tissue barriers · 2018Review
- Cell-cell adhesion accounts for the different orientation of columnar and hepatocytic cell divisions.The Journal of cell biology · 2017Article
- Article
- Functional characterization of AMP-activated protein kinase signaling in tumorigenesis.Biochimica et biophysica acta · 2016Review
- Deletion of Lkb1 in adult mice results in body weight reduction and lethality.Scientific reports · 2016Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
unlabelledLiver 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 examination revealed that hepatocyte apical membrane with microvilli substantially extended into the basolateral domain of LKB1(-/-) livers. Immunofluorescence studies revealed that loss of LKB1 led to longer and wider canalicular structures correlating with mislocalization of the junctional protein, cingulin. To test junctional function, we used intravital microscopy to quantify the transport kinetics of 6-carboxyfluorescein 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 remained largely in hepatocytes, canalicular secretion was delayed, and 6-CF appeared in the blood. To test whether 6-CF was transported through permeable TJ, we intravenously injected low molecular weight (3 kDa) dextran in combination with 6-CFDA. In wild-type mice, 3 kDa 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.
conclusionLKB1 plays a critical role in regulating the 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. (Hepatology 2016;64:1317-1329).
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