PDF(Pubmed)
Abstract：
The liver is a remarkable organ that can regenerate in response to injury. Depending on the extent of injury, the liver can undergo compensatory hyperplasia or fibrosis. Despite decades of research, the molecular mechanisms underlying these processes are poorly understood. Here, we developed a new model to study liver regeneration based on cryoinjury. To visualise liver regeneration at cellular resolution, we adapted the CUBIC tissue-clearing approach. Hepatic cryoinjury induced a localised necrotic and apoptotic lesion characterised by inflammation and infiltration of innate immune cells. After this initial phase, we observed fibrosis, which resolved as regeneration re-established homeostasis in 30 days. Importantly, this approach enables the comparison of healthy and injured parenchyma within an individual animal, providing unique advantages to previous models. In summary, the hepatic cryoinjury model provides a fast and reproducible method for studying the cellular and molecular pathways underpinning fibrosis and liver regeneration.
摘要：
肝脏是一个非凡的器官，可以响应损伤而再生。根据受伤的程度,肝脏可以发生代偿性增生或纤维化。尽管经过几十年的研究,这些过程背后的分子机制知之甚少。这里,我们开发了一种基于冷冻损伤的肝再生研究新模型。以细胞分辨率可视化肝脏再生，我们采用了CUBIC组织清除方法。肝冷冻损伤引起局部坏死和凋亡性病变，其特征是炎症和先天性免疫细胞浸润。在这个初始阶段之后，我们观察到纤维化，它在30天内恢复为再生重建的体内平衡。重要的是,这种方法可以将健康和受伤的薄壁组织与单个动物进行比较，为以前的型号提供独特的优势。总之,肝冷冻损伤模型为研究支持纤维化和肝再生的细胞和分子途径提供了一种快速且可重复的方法。
