Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Vet Q. 2021 Dec;41(1):172-180. doi: 10.1080/01652176.2021.1923085.
The Hippo pathway is a highly conserved kinase cascade in mammals with the proteins YAP and TAZ as its most important downstream effectors that shuttle between cytoplasma and nucleus. It has a crucial role in processes such as embryogenesis, organ size control, homeostasis and tissue regeneration, where mechanosensing and/or cell-cell interactions are involved. As the pathway is associated with many essential functions in the body, its dysregulation is related to many diseases. In contrast to human pathology, a PubMed-search on Hippo, YAP/TAZ and companion animals (horse, equine, dog, canine, cat, feline) retrieved few publications. Because of its high level of functional conservation, it is anticipated that also in veterinary sciences aberrant Hippo YAP/TAZ signaling would be implicated in animal pathologies. Publications on Hippo YAP/TAZ in companion animals are mainly in cats and dogs and related to oncology. Here, we emphasize the important role of YAP/TAZ in liver diseases. First the liver has a remarkable regeneration capacity and a strict size control and the liver has a moderate liver cell renewal (homeostasis). The last years numerous papers show the importance of YAP/TAZ in hepatocellular carcinoma (HCC), hepatocyte differentiation and bile duct epithelial (BEC) cell survival. YAP/TAZ signaling is involved in activation of hepatic stellate cells crucial in fibrogenesis. The availability of drugs (e.g. verteporfin) targeting the YAP/TAZ pathway are described as is their potential usage in veterinary medicine. The aim of this overview is to stimulate researchers' and clinicians' interest in the potential role of Hippo YAP/TAZ signaling in veterinary medicine.
Hippo 通路是一种高度保守的激酶级联反应，在哺乳动物中，其最重要的下游效应物是 YAP 和 TAZ，它们在细胞质和细胞核之间穿梭。它在胚胎发生、器官大小控制、内稳态和组织再生等过程中起着至关重要的作用，其中涉及机械感知和/或细胞-细胞相互作用。由于该通路与体内许多重要功能有关，其失调与许多疾病有关。与人类病理学相比，在 PubMed 上对 Hippo、YAP/TAZ 和伴侣动物（马、马科、狗、犬科、猫、猫科）进行搜索，检索到的相关出版物很少。由于其功能高度保守，预计在兽医科学中，异常的 Hippo YAP/TAZ 信号也会涉及动物病理学。关于伴侣动物 Hippo YAP/TAZ 的出版物主要集中在猫和狗上，与肿瘤学有关。在这里，我们强调 YAP/TAZ 在肝脏疾病中的重要作用。首先，肝脏具有显著的再生能力和严格的大小控制，肝脏具有适度的肝细胞更新（内稳态）。近年来，大量论文表明 YAP/TAZ 在肝细胞癌（HCC）、肝细胞分化和胆管上皮（BEC）细胞存活中的重要作用。YAP/TAZ 信号参与激活肝星状细胞，这对纤维化至关重要。描述了靶向 YAP/TAZ 通路的药物（如 verteporfin）的可用性及其在兽医医学中的潜在用途。本综述的目的是激发研究人员和临床医生对 Hippo YAP/TAZ 信号在兽医医学中的潜在作用的兴趣。
