Limits...
Structural and functional hepatocyte polarity and liver disease.

Gissen P, Arias IM - J. Hepatol. (2015)

Bottom Line: Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus.However, the molecular mechanisms underlying these defects are not well understood.Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, UK; UCL Institute of Child Health, London, UK; Great Ormond Street Hospital, London, UK. Electronic address: p.gissen@ucl.ac.uk.

No MeSH data available.


Related in: MedlinePlus

Signaling pathways in hepatocyte polarity. The relation between LKB1, AMPK and hepatocellular polarization is schematized based on experimental observations in sandwich cultured mouse hepatocytes (adapted from Homolya et al., 2014) [22]. AMPK activation inhibits processes which utilize ATP with the exception of polarization machinery. In addition, protein catabolism is enhanced. How LKB1 participates in polarization and apical trafficking of ABCB11 and other ABC transporters is not known; however, the process is associated with AMPK activation and canalicular network formation. Taurocholate stimulates microtubular-dependent trafficking by activating the cAMP-Epac pathway, whereas, in Lkb1−/− mice, the stimulating effect of taurocholate and Epac is prevented; however, cAMP activation restores intracellular trafficking by a PKA-dependent mechanism which is independent of AMPK. PP2C-protein phosphatase 2C removes phosphate from phosphor-AMPK. AICAR activates AMPK in a manner similar to cAMP.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4582071&req=5

f0020: Signaling pathways in hepatocyte polarity. The relation between LKB1, AMPK and hepatocellular polarization is schematized based on experimental observations in sandwich cultured mouse hepatocytes (adapted from Homolya et al., 2014) [22]. AMPK activation inhibits processes which utilize ATP with the exception of polarization machinery. In addition, protein catabolism is enhanced. How LKB1 participates in polarization and apical trafficking of ABCB11 and other ABC transporters is not known; however, the process is associated with AMPK activation and canalicular network formation. Taurocholate stimulates microtubular-dependent trafficking by activating the cAMP-Epac pathway, whereas, in Lkb1−/− mice, the stimulating effect of taurocholate and Epac is prevented; however, cAMP activation restores intracellular trafficking by a PKA-dependent mechanism which is independent of AMPK. PP2C-protein phosphatase 2C removes phosphate from phosphor-AMPK. AICAR activates AMPK in a manner similar to cAMP.

Mentions: Embryologically, hepatoblasts are non-polarized and give rise to hepatocytes on stimulation by Oncostatin M (OSM) and TNF-alpha, and cholangiocytes, which are signaled by NOTCH and TGF-beta [11–13]. In mice, hepatocytes begin polarization on fetal day 14; however, mature BC do not appear until fetal day 21 [14,15]. Early canalicular network occurs by day 20 and rapid postnatal network formation occurs within two-three days after birth. During development, tight junctional complexes form, and apical and basolateral proteins including transporters become associated with specific plasma membrane domains (Fig. 3) [16]. These changes are associated with activation of 7-alpha-hydroxylase and synthesis of bile acids which may participate in regulating canalicular network formation similar to effects observed in hepatocyte cultures in which bile acids acting through a cAMP-Epac-MEK-AMPK pathway accelerate canalicular network formation (Fig. 4) [7].


Structural and functional hepatocyte polarity and liver disease.

Gissen P, Arias IM - J. Hepatol. (2015)

Signaling pathways in hepatocyte polarity. The relation between LKB1, AMPK and hepatocellular polarization is schematized based on experimental observations in sandwich cultured mouse hepatocytes (adapted from Homolya et al., 2014) [22]. AMPK activation inhibits processes which utilize ATP with the exception of polarization machinery. In addition, protein catabolism is enhanced. How LKB1 participates in polarization and apical trafficking of ABCB11 and other ABC transporters is not known; however, the process is associated with AMPK activation and canalicular network formation. Taurocholate stimulates microtubular-dependent trafficking by activating the cAMP-Epac pathway, whereas, in Lkb1−/− mice, the stimulating effect of taurocholate and Epac is prevented; however, cAMP activation restores intracellular trafficking by a PKA-dependent mechanism which is independent of AMPK. PP2C-protein phosphatase 2C removes phosphate from phosphor-AMPK. AICAR activates AMPK in a manner similar to cAMP.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582071&req=5

f0020: Signaling pathways in hepatocyte polarity. The relation between LKB1, AMPK and hepatocellular polarization is schematized based on experimental observations in sandwich cultured mouse hepatocytes (adapted from Homolya et al., 2014) [22]. AMPK activation inhibits processes which utilize ATP with the exception of polarization machinery. In addition, protein catabolism is enhanced. How LKB1 participates in polarization and apical trafficking of ABCB11 and other ABC transporters is not known; however, the process is associated with AMPK activation and canalicular network formation. Taurocholate stimulates microtubular-dependent trafficking by activating the cAMP-Epac pathway, whereas, in Lkb1−/− mice, the stimulating effect of taurocholate and Epac is prevented; however, cAMP activation restores intracellular trafficking by a PKA-dependent mechanism which is independent of AMPK. PP2C-protein phosphatase 2C removes phosphate from phosphor-AMPK. AICAR activates AMPK in a manner similar to cAMP.
Mentions: Embryologically, hepatoblasts are non-polarized and give rise to hepatocytes on stimulation by Oncostatin M (OSM) and TNF-alpha, and cholangiocytes, which are signaled by NOTCH and TGF-beta [11–13]. In mice, hepatocytes begin polarization on fetal day 14; however, mature BC do not appear until fetal day 21 [14,15]. Early canalicular network occurs by day 20 and rapid postnatal network formation occurs within two-three days after birth. During development, tight junctional complexes form, and apical and basolateral proteins including transporters become associated with specific plasma membrane domains (Fig. 3) [16]. These changes are associated with activation of 7-alpha-hydroxylase and synthesis of bile acids which may participate in regulating canalicular network formation similar to effects observed in hepatocyte cultures in which bile acids acting through a cAMP-Epac-MEK-AMPK pathway accelerate canalicular network formation (Fig. 4) [7].

Bottom Line: Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus.However, the molecular mechanisms underlying these defects are not well understood.Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, UK; UCL Institute of Child Health, London, UK; Great Ormond Street Hospital, London, UK. Electronic address: p.gissen@ucl.ac.uk.

No MeSH data available.


Related in: MedlinePlus