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During liver fibrosis progression, the nerve terminals behind the sympathetic ganglion release NE, which binds to the α-adrenergic receptors on the surface of HSCs, triggering downstream Ca 2+ mobilization, ERK1/2 and PI3K/Akt phosphorylation cascades, further upregulating the expression of TGFβ, enhancing the transcriptional activity of pro-fibrotic genes, thereby stimulating collagen deposition and the expression of α-SMA, and accelerating liver fibrosis [16–19]
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Despite extensive studies on KARs, a fundamental question remains unresolved: why do KARs require large conformational changes upon desensitization
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