Okamura Daryl M, Brewer Chris M, Wakenight Paul, Bahrami Nadia, Bernardi Kristina, Tran Amy, Olson Jill, Shi Xiaogang, Yeh Szu-Ying, Piliponsky Adrian, Collins Sarah J, Nguyen Elizabeth D, Timms Andrew E, MacDonald James W, Bammler Theo K, Nelson Branden R, Millen Kathleen J, Beier David R, Majesky Mark W
Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Center for Developmental Biology & Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98105, USA.
iScience. 2021 Nov 3;24(11):103269. doi: 10.1016/j.isci.2021.103269. eCollection 2021 Nov 19.
Fibrosis-driven solid organ failure is an enormous burden on global health. Spiny mice () are terrestrial mammals that can regenerate severe skin wounds without scars to avoid predation. Whether spiny mice also regenerate internal organ injuries is unknown. Here, we show that despite equivalent acute obstructive or ischemic kidney injury, spiny mice fully regenerate nephron structure and organ function without fibrosis, whereas C57Bl/6 or CD1 mice progress to complete organ failure with extensive renal fibrosis. Two mechanisms for vertebrate regeneration have been proposed that emphasize either extrinsic (pro-regenerative macrophages) or intrinsic (surviving cells of the organ itself) controls. Comparative transcriptome analysis revealed that the genome appears poised at the time of injury to initiate regeneration by surviving kidney cells, whereas macrophage accumulation was not detected until about day 7. Thus, we provide evidence for rapid activation of a gene expression signature for regenerative wound healing in the spiny mouse kidney.
纤维化驱动的实体器官衰竭给全球健康带来了巨大负担。刺毛鼠是一种陆生哺乳动物，能够再生严重的皮肤伤口且不留疤痕，以避免被捕食。刺毛鼠是否也能再生内部器官损伤尚不清楚。在这里，我们表明，尽管刺毛鼠和C57Bl/6或CD1小鼠遭受了同等程度的急性梗阻性或缺血性肾损伤，但刺毛鼠能完全再生肾单位结构和器官功能且不发生纤维化，而C57Bl/6或CD1小鼠则会发展为完全性器官衰竭并伴有广泛的肾纤维化。关于脊椎动物再生提出了两种机制，一种强调外在控制（促再生巨噬细胞），另一种强调内在控制（器官自身存活细胞）。比较转录组分析显示，刺毛鼠基因组在损伤时似乎已做好准备，由存活的肾细胞启动再生，而直到大约第7天才检测到巨噬细胞的积累。因此，我们为刺毛鼠肾脏中再生性伤口愈合的基因表达特征的快速激活提供了证据。
