A variety of G protein-coupled receptors (GPCRs) have been implicated in the pathogenesis of pulmonary fibrosis, largely through their promotion of profibrotic fibroblast activation. By contrast, recent work has highlighted the beneficial effects of Gαs-coupled GPCRs on reducing fibroblast activation and fibrosis. This review highlights how fibrosis-promoting and -inhibiting GPCR signaling converges on downstream signaling and transcriptional effectors, and how the diversity and dynamics of GPCR expression challenge efforts to identify effective therapies for idiopathic pulmonary fibrosis (IPF). Next-generation strategies to overcome these challenges, focusing on target selection, polypharmacology, and personalized medicine approaches, are discussed as a path towards more effective GPCR-targeted therapies for pulmonary fibrosis.

中文翻译：

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靶向 GPCR 信号用于特发性肺纤维化治疗。

多种 G 蛋白偶联受体 (GPCR) 与肺纤维化的发病机制有关，主要是通过它们促进促纤维化成纤维细胞活化。相比之下，最近的工作强调了 Gαs 偶联 GPCR 在减少成纤维细胞活化和纤维化方面的有益作用。本综述重点介绍了促进纤维化和抑制纤维化的 GPCR 信号如何融合到下游信号和转录效应子上，以及 GPCR 表达的多样性和动态如何挑战确定特发性肺纤维化 (IPF) 有效疗法的努力。克服这些挑战的下一代策略，侧重于靶点选择、多药理学和个性化医疗方法，被讨论为通向更有效的 GPCR 靶向肺纤维化疗法的途径。