Key result
β3-AR promotes cardiac fibrosis through β-arrestin2-mediated biased activation of the JNK/c-Jun/TGF-β1 pathway, independent of classical Gi signalling.
Why the study?
β3-adrenergic receptor has controversial roles in cardiac remodelling, and its pro-fibrotic mechanism in cardiac fibroblasts and link to β-arrestin2-mediated biased activation remained unclear.
Population
Primary cardiac fibroblasts isolated from neonatal C57BL/6 mice
Comparison
β3-AR overexpression, agonist stimulation, antagonist inhibition, JNK inhibitor, or β-arrestin2 knockdown
Design
Preclinical in vitro laboratory study
Authors
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β3-AR pro-fibrotic effects in fibroblasts warrant caution in HF models; hypothesis-generating for remodeling therapies, clinical translation remains open.
β3-AR promotes cardiac fibrosis through β-arrestin2-mediated biased activation of the JNK/c-Jun/TGF-β1 pathway, revealing a novel mechanism and potential therapeutic target for myocardial fibrosis and heart failure.
Xu et al. (2026) studied Myocardial fibrosis. β3-AR activation (BRL37344) and overexpression vs. Control, antagonist (SR59230A), JNK inhibitor (SP600125), or β-arrestin2 knockdown was evaluated on Fibrosis markers (α-SMA, FN, collagen I/III) and TGF-β1 expression. β3-AR promotes cardiac fibrosis through β-arrestin2-mediated biased activation of the JNK/c-Jun/TGF-β1 pathway, independent of classical Gi signalling.
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