In:
BioMed Research International, Hindawi Limited, Vol. 2020 ( 2020-08-05), p. 1-14
Abstract:
There remain few data about the role of homeostatic compaction in hepatic polarization. A previous study has found that mechanical compaction can accelerate hepatocyte polarization; however, the cellular mechanism underlying the effect is mostly unclear. Hepatocyte nuclear factor 4 alpha (HNF4 α ) is crucial for hepatic polarization in liver morphogenesis. Therefore, we sought to identify any possible involvement of HNF4 α in the process of hepatocyte polarization accelerated by mechanical compaction. We first verified in the nonhepatic cell model HEK-293T, and the hepatic cell model primary hepatocytes that the mechanical compaction on cell aggregates simulated by using transient centrifugation can directly activate the expression of HNF4 α promoters. Moreover, data using primary hepatocytes showed that the HNF4 α expression is positively associated with the levels of compaction force: 2.1-folds higher at the mRNA level and 2.1-folds higher at the protein level for 500 g vs. 0 g. Furthermore, activated HNF4 α expression is associated with the enhanced biliary canalicular formation and the increased production of albumin and urea. Pretreatment with Latrunculin B, an inhibitor of F-actin, and SHE78-7, an inhibitor of E-cadherin, which both interrupt the pathway of mechanical transduction, partially but significantly reduced the HNF4 α expression and production of albumin and urea. In conclusion, HNF4 α can be actively involved in the hepatic polarization in the context of environmental mechanical compaction.
Type of Medium:
Online Resource
ISSN:
2314-6133
,
2314-6141
DOI:
10.1155/2020/8016306
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2020
detail.hit.zdb_id:
2698540-8
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