The importance of cyclic adenosine monophosphate (cAMP) in cellular responses to extracellular signals is well established. Many years after discovery, our understanding of the intricacy of cAMP signaling has improved dramatically. Multiple layers of regulation exist to ensure the specificity of cellular cAMP signaling. Hence, disturbances in cAMP homeostasis could arise at multiple levels, from changes in G protein coupled receptors and production of cAMP to the rate of degradation by phosphodiesterases. cAMP signaling plays critical roles in metabolism, inflammation and development of fibrosis in several tissues. Alcohol-associated liver disease (ALD) is a multifactorial condition ranging from a simple steatosis to steatohepatitis and fibrosis and ultimately cirrhosis, which might lead to hepatocellular cancer. To date, there is no FDA-approved therapy for ALD. Hence, identifying the targets for the treatment of ALD is an important undertaking. Several human studies have reported the changes in cAMP homeostasis in relation to alcohol use disorders. cAMP signaling has also been extensively studied in in vitro and in vivo models of ALD. This review focuses on the role of cAMP in the pathobiology of ALD with emphasis on the therapeutic potential of targeting cAMP signaling for the treatment of various stages of ALD.

中文翻译：

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酒精相关肝病病理生物学中的 cAMP 信号

环磷酸腺苷 (cAMP) 在细胞对细胞外信号的反应中的重要性已得到充分证实。发现多年后，我们对复杂的 cAMP 信号的理解有了显着提高。存在多层调节以确保细胞 cAMP 信号的特异性。因此，从 G 蛋白偶联受体的变化和 cAMP 的产生到磷酸二酯酶的降解速率，cAMP 稳态的紊乱可能出现在多个层面。cAMP 信号传导在多种组织的代谢、炎症和纤维化发展中起着关键作用。酒精相关性肝病 (ALD) 是一种多因素疾病，从简单的脂肪变性到脂肪性肝炎和纤维化，再到最终可能导致肝细胞癌的肝硬化。迄今为止，没有 FDA 批准的 ALD 疗法。因此，确定治疗 ALD 的目标是一项重要的工作。几项人类研究报告了与酒精使用障碍相关的 cAMP 稳态变化。cAMP 信号转导也在 ALD 的体外和体内模型中得到了广泛研究。本综述重点关注 cAMP 在 ALD 病理生物学中的作用，重点是靶向 cAMP 信号传导治疗 ALD 各个阶段的治疗潜力。