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Promotion of NR1I3-mediated liver growth is accompanied by STAT3 activation

Mark E Mazin1,2, Andrei A Yarushkin2, Yuliya A Pustylnyak1

  • 1Novosibirsk State University, Pirogova Street, 1, Novosibirsk, Russia, 630090.

Molecular Biology Reports
|March 19, 2022
PubMed
Abstract

Insights

The constitutive androstane receptor (CAR) activates STAT3 signaling, promoting liver growth and hepatocyte proliferation. This pathway involves key targets like cMyc and Cyclin D1.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Endocrinology

Background:

  • The precise mechanisms of constitutive androstane receptor (CAR, NR1I3) in regulating liver growth and hepatocyte proliferation remain incompletely understood.
  • This study investigated the potential activation of STAT3 by CAR signaling within the mouse liver.

Purpose of the Study:

  • To elucidate the role of STAT3 activation in CAR-mediated liver growth.
  • To determine if CAR signaling in vivo can activate STAT3 in hepatocytes.

Main Methods:

  • Western blot analysis
  • Immunofluorescence assays
  • Real-time PCR in mouse liver models
  • Treatment with CAR agonist TCPOBOP

Main Results:

  • CAR activation by TCPOBOP induced STAT3 phosphorylation and nuclear translocation in mouse liver.
  • CAR-mediated STAT3 activation promoted hepatocyte proliferation and liver growth.
  • Upregulation of cMyc and Cyclin D1 was observed, partially mediating the proliferative effects of the CAR-STAT3 pathway.

Conclusions:

  • CAR-activated STAT3 signaling contributes to TCPOBOP-induced liver growth and hepatocyte proliferation.
  • The molecular targets cMyc and Cyclin D1 are implicated in the CAR-STAT3 pathway's proliferative effects.
Keywords:
CARHepatocyte proliferationLiverLiver hyperplasiaSTAT3

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