Department of Physiology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; email:
Medical Scientist Training Program, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Annu Rev Pathol. 2021 Jan 24;16:299-322. doi: 10.1146/annurev-pathol-030420-105050. Epub 2020 Nov 24.
Studies of the regenerative capacity of the liver have converged on the Hippo pathway, a serine/threonine kinase cascade discovered in and conserved from unicellular organisms to mammals. Genetic studies of mouse and rat livers have revealed that the Hippo pathway is a key regulator of liver size, regeneration, development, metabolism, and homeostasis and that perturbations in the Hippo pathway can lead to the development of common liver diseases, such as fatty liver disease and liver cancer. In turn, pharmacological targeting of the Hippo pathway may be utilized to boost regeneration and to prevent the development and progression of liver diseases. We review current insights provided by the Hippo pathway into liver pathophysiology. Furthermore, we present a path forward for future studies to understand how newly identified components of the Hippo pathway may control liver physiology and how the Hippo pathway is regulated in the liver.
对肝脏再生能力的研究已经集中在 Hippo 通路，这是一种在 中发现的丝氨酸/苏氨酸激酶级联反应，从单细胞生物到哺乳动物都保守存在。对小鼠和大鼠肝脏的遗传研究表明，Hippo 通路是肝脏大小、再生、发育、代谢和内稳态的关键调节剂，Hippo 通路的扰动可能导致常见肝脏疾病的发展，如脂肪肝和肝癌。反过来，Hippo 通路的药理学靶向可能被用于促进再生，并预防肝脏疾病的发生和进展。我们综述了 Hippo 通路为肝脏病理生理学提供的最新见解。此外，我们为未来的研究提出了一个前进的方向，以了解 Hippo 通路的新鉴定成分如何控制肝脏生理学以及 Hippo 通路在肝脏中是如何被调控的。
