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β₂-adrenergic receptor promotes liver regeneration partially through crosstalk with c-met.

ABSTRACT: The β₂-adrenergic receptor (β₂AR) is a G protein-coupled receptor (GPCR) that mediates the majority of cellular responses to external stimuli. Aberrant expression of β₂AR results in various pathophysiological disorders, including tumorigenesis, but little is known about its role in liver regeneration. This study aims to investigate the impact and the underlying mechanism of β₂AR in liver regeneration. Here, we found that β₂AR was upregulated during liver regeneration induced by 70% PH. Deletion of β₂AR in mice resulted in 62% mortality 2 days post-PH, decreased proliferative marker expression and impaired liver function throughout regeneration. Moreover, AAV8-mediated overexpression of β₂AR in hepatocytes accelerated the regeneration process and increased target gene expression. Mechanistically, β₂AR recruited G-protein-coupled receptor kinase 2 (GRK2) to the membrane and then formed a complex with c-met to transactivate c-met signaling, which triggered downstream extracellular regulated protein kinase (ERK) signaling activation and nuclear translocation. Inhibition of c-met with SU11274 or ERK with U0126 decreased β₂AR overexpression-induced hepatocyte proliferation. Our findings revealed that β₂AR might act as a critical mediator regulating liver regeneration by crosstalk with c-met and activation of ERK signaling.

SUBMITTER: Tao X

PROVIDER: S-EPMC9237079 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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β2-adrenergic receptor promotes liver regeneration partially through crosstalk with c-met.

Tao Xiang X Chen Can C Chen Yingxiang Y Zhang Luoying L Hu Jiong J Yu Hongjun H Liang Minglu M Fu Qin Q Huang Kai K

Cell death & disease 20220627 6

The β2-adrenergic receptor (β2AR) is a G protein-coupled receptor (GPCR) that mediates the majority of cellular responses to external stimuli. Aberrant expression of β2AR results in various pathophysiological disorders, including tumorigenesis, but little is known about its role in liver regeneration. This study aims to investigate the impact and the underlying mechanism of β2AR in liver regeneration. Here, we found that β2AR was upregulated ...[more]

PMID: 35760785

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β₂-adrenergic receptor promotes liver regeneration partially through crosstalk with c-met.

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β<sub>2</sub>-adrenergic receptor promotes liver regeneration partially through crosstalk with c-met.

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