Zheng Hanxue, Liu Hongbo, Xu Qian, Wang Wenjun, Li Linfeng, Ye Gang, Wen Xiaomin, Chen Fulin, Yu Yuan
Laboratory of Tissue Engineering, College of Life Sciences, Northwest University, Xi'an, China.
Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, Xi'an, China.
Front Cell Dev Biol. 2021 Aug 6;9:649656. doi: 10.3389/fcell.2021.649656. eCollection 2021.
Phosphatidylinositol 3-kinase (PI3K) signaling plays a central role in various biological processes, and its abnormality leads to a broad spectrum of human diseases, such as cancer, fibrosis, and immunological disorders. However, the mechanisms by which PI3K signaling regulates the behavior of stem cells during regeneration are poorly understood. Planarian flatworms possess abundant adult stem cells (called neoblasts) allowing them to develop remarkable regenerative capabilities, thus the animals represent an ideal model for studying stem cells and regenerative medicine . In this study, the spatiotemporal expression pattern of , a PI3K ortholog in the planarian , was investigated and suggests its potential role in wound response and tissue regeneration. A loss-of-function study was conducted using small molecules and RNA interference technique, providing evidence that PI3K signaling is required for blastema regrowth and cilia maintenance during planarian regeneration and homeostasis. Interestingly, the mitotic and apoptotic responses to amputation are substantially abated in PI3K inhibitor-treated regenerating animals, while knockdown of alleviates the mitotic response and postpones the peak of apoptotic cell death, which may contribute to the varying degrees of regenerative defects induced by the pharmacological and genetic approaches. These observations reveal novel roles for PI3K signaling in the regulation of the cellular responses to amputation during planarian regeneration and provide insights for investigating the disease-related genes in the regeneration-competent organism .
磷脂酰肌醇3激酶（PI3K）信号传导在各种生物学过程中起着核心作用，其异常会导致多种人类疾病，如癌症、纤维化和免疫紊乱。然而，PI3K信号传导在再生过程中调节干细胞行为的机制尚不清楚。涡虫扁虫拥有丰富的成体干细胞（称为新细胞），使其具有显著的再生能力，因此这种动物是研究干细胞和再生医学的理想模型。在本研究中，对涡虫中PI3K直系同源物的时空表达模式进行了研究，并表明其在伤口反应和组织再生中的潜在作用。使用小分子和RNA干扰技术进行了功能丧失研究，提供了证据表明PI3K信号传导是涡虫再生和体内平衡过程中芽基再生和纤毛维持所必需的。有趣的是，在PI3K抑制剂处理的再生动物中，对截肢的有丝分裂和凋亡反应显著减弱，而敲低则减轻了有丝分裂反应并推迟了凋亡细胞死亡的峰值，这可能导致了药理学和遗传学方法诱导的不同程度的再生缺陷。这些观察结果揭示了PI3K信号传导在涡虫再生过程中调节对截肢的细胞反应中的新作用，并为研究具有再生能力的生物体中的疾病相关基因提供了见解。
