PhD Scientific Days 2025

Molecular Medicine IV.

Crosstalk of LKB1- and PKA-dependent signaling pathways in the regulation of hepatocyte polarity

Előadó neve

Körmendi Petra, MSc

Neptun code

H3COFX

Előadó munkahelye

HUN-REN Research Centre for Natural Sciences

Előadó telefonszáma

+36302495687

Előadó e-mail címe

petra.bianka.kormendi@gmail.com

Az előadás címe

Crosstalk of LKB1- and PKA-dependent signaling pathways in the regulation of hepatocyte polarity

Szerző(k) neve és munkahelye

Petra Körmendi¹, Ágnes Telbisz¹, Anikó Zeöld², László Homolya¹

1: HUN-REN Research Centre for Natural Sciences
2: Semmelweis University

Bemutatás módja

Szóbeli

Szekció

Molecular Medicine IV.

Language of the presentation

English

Preferred session

Molecular Medicine

Összefoglaló szövege

Cell polarization is an essential part of the development of a functional liver cell. The bile canaliculi begin to form on the apical side of two adjacent liver cells, then interconnect and develop into a canalicular network. The presence of a functional canalicular network is essential for most hepatic functions including bile secretion, cholesterol metabolism, detoxification, etc. Disruption of canalicular secretion can cause intrahepatic cholestasis by bile salt accumulation, which can lead to inflammation, fibrosis, or even liver failure. Hepatocyte polarization and its regulation are therefore of great medical importance.
The key role of tumor-suppressor liver kinase B1 (LKB1) in hepatocyte polarization has long been known. Bile acids, such as taurocholate (TC), stimulate canalicular network formation via LKB1/AMPK-dependent signaling pathway. We have previously shown an essential role for LKB1 in the regulation of polarized trafficking of canalicular membrane proteins and have also revealed the existence of a collateral PKA-dependent signaling pathway. In the present work, we investigated whether PKA also influences canalicular network formation and whether there is a crosstalk between the two pathways. For this purpose, we monitored the in vitro repolarization process of the human hepatic model HepaRG cells and isolated rat primary hepatocytes by Western blot analysis and immunofluorescence microscopy. The cells were treated with TC, the cAMP-elevating agent forskolin, and the PKA activator 6-benzoyl-cAMP (6Bnz). Our results showed that specific activation of PKA stimulates canalicular network formation and demonstrated a crosstalk between the two signaling pathways: activation of PKA leads to phosphorylation of LKB1 and stimulation of downstream processes, such as development of bile canaliculi. LKB1 knockdown experiments clearly demonstrated the LKB1-dependence of this stimulation. Our results may help to understand the molecular mechanisms responsible for the pathogenesis of diseases involving hepatocyte polarity and thus help to identify novel therapeutic targets for the treatment of liver diseases.
This work has been supported by the National Research, Development and Innovation Office (grant number: OKTA K-128123)

University

Semmelweis University

Supervisor

László Homolya

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem hagyta jóvá

Előadó

4752

Start

16:00

End

16:15