Tang Weifeng, Li Min, Yangzhong Xiaoting, Zhang Xifeng, Zu Anju, Hou Yunjiao, Li Lin, Sun Shibo
Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital, Kunming Medical University, Kunming, China.
Clinical Medicine, Seven class, 2019 Grade, Kunming Medical University, Kunming, China.
Cell Death Discov. 2022 Apr 20;8(1):213. doi: 10.1038/s41420-022-01020-6.
The hippo signaling pathway is a highly conserved evolutionary signaling pathway that plays an important role in regulating cell proliferation, organ size, tissue development, and regeneration. Increasing evidences consider that the hippo signaling pathway is involved in the process of respiratory diseases. Hippo signaling pathway is mainly composed of mammalian STE20-like kinase 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), WW domain of the Sav family containing protein 1 (SAV1), MOB kinase activator 1 (MOB1), Yes-associated protein (YAP) or transcriptional coactivator with PDZ-binding motif (TAZ), and members of the TEA domain (TEAD) family. YAP is the cascade effector of the hippo signaling pathway. The activation of YAP promotes pulmonary arterial vascular smooth muscle cells (PAVSMCs) proliferation, which leads to pulmonary vascular remodeling; thereby the pulmonary arterial hypertension (PAH) is aggravated. While the loss of YAP leads to high expression of inflammatory genes and the accumulation of inflammatory cells, the pneumonia is consequently exacerbated. In addition, overexpressed YAP promotes the proliferation of lung fibroblasts and collagen deposition; thereby the idiopathic pulmonary fibrosis (IPF) is promoted. Moreover, YAP knockout reduces collagen deposition and the senescence of adult alveolar epithelial cells (AECs); hence the IPF is slowed. In addition, hippo signaling pathway may be involved in the repair of acute lung injury (ALI) by promoting the proliferation and differentiation of lung epithelial progenitor cells and intervening in the repair of pulmonary capillary endothelium. Moreover, the hippo signaling pathway is involved in asthma. In conclusion, the hippo signaling pathway is involved in respiratory diseases. More researches are needed to focus on the molecular mechanisms by which the hippo signaling pathway participates in respiratory diseases.
河马信号通路是一条高度保守的进化信号通路，在调节细胞增殖、器官大小、组织发育和再生中发挥重要作用。越来越多的证据表明，河马信号通路参与呼吸系统疾病的发生过程。河马信号通路主要由哺乳动物STE20样激酶1/2（MST1/2）、大肿瘤抑制因子1/2（LATS1/2）、含WW结构域的Sav家族蛋白1（SAV1）、MOB激酶激活剂1（MOB1）、Yes相关蛋白（YAP）或含PDZ结合基序的转录共激活因子（TAZ）以及TEA结构域（TEAD）家族成员组成。YAP是河马信号通路的级联效应器。YAP的激活促进肺动脉血管平滑肌细胞（PAVSMC）增殖，导致肺血管重塑，从而加重肺动脉高压（PAH）。而YAP缺失则导致炎症基因高表达和炎症细胞积聚，进而加剧肺炎。此外，YAP过表达促进肺成纤维细胞增殖和胶原蛋白沉积，从而促进特发性肺纤维化（IPF）。而且，YAP基因敲除减少胶原蛋白沉积和成年肺泡上皮细胞（AEC）衰老，因此减缓IPF进程。此外，河马信号通路可能通过促进肺上皮祖细胞增殖和分化以及干预肺毛细血管内皮修复参与急性肺损伤（ALI）的修复。而且，河马信号通路还参与哮喘。总之，河马信号通路参与呼吸系统疾病。需要更多研究关注河马信号通路参与呼吸系统疾病的分子机制。
