美国耶鲁大学Stefan Somlo研究小组通过逆转小鼠的多囊肾疾病揭示肾脏的可塑性。该项研究成果于2021年10月11日在线发表在《自然—遗传学》杂志上。

研究人员构建了一个小鼠模型，其中任一Pkd基因的成年失活可以在以后的时间里重新激活该基因。利用这个模型，研究人员表明，Pkd基因在囊性肾脏中的重新表达导致常染色体显性多囊肾病（ADPKD）的快速逆转。囊肿细胞增殖减少，自噬作用被激活，由鳞状细胞内衬的管腔扩大的囊肿小管恢复到由立方体细胞内衬的正常管腔。炎症、细胞外基质沉积和肌成纤维细胞激活的增加被逆转，而且肾脏变得更小。

研究人员的结论是，ADPKD的表型特征是可逆的，肾脏有一种意想不到的可塑性能力，至少部分受ADPKD基因功能控制。

据介绍，在ADPKD中，当肾小管细胞因体细胞"二次打击"突变而导致PKD1或PKD2无效时，囊肿就开始形成。随后的囊肿进展通过肾小管细胞形状、增殖和分泌的变化重塑了器官。肾脏出现炎症和纤维化。

附：英文原文

Title: Renal plasticity revealed through reversal of polycystic kidney disease in mice

Author: Dong, Ke, Zhang, Chao, Tian, Xin, Coman, Daniel, Hyder, Fahmeed, Ma, Ming, Somlo, Stefan

Issue&Volume: 2021-10-11

Abstract: Initiation of cyst formation in autosomal dominant polycystic kidney disease (ADPKD) occurs when kidney tubule cells are rendered null for either PKD1 or PKD2 by somatic ‘second hit’ mutations. Subsequent cyst progression remodels the organ through changes in tubule cell shape, proliferation and secretion. The kidney develops inflammation and fibrosis. We constructed a mouse model in which adult inactivation of either Pkd gene can be followed by reactivation of the gene at a later time. Using this model, we show that re-expression of Pkd genes in cystic kidneys results in rapid reversal of ADPKD. Cyst cell proliferation is reduced, autophagy is activated and cystic tubules with expanded lumina lined by squamoid cells revert to normal lumina lined by cuboidal cells. Increases in inflammation, extracellular matrix deposition and myofibroblast activation are reversed, and the kidneys become smaller. We conclude that phenotypic features of ADPKD are reversible and that the kidney has an unexpected capacity for plasticity controlled at least in part by ADPKD gene function.

DOI: 10.1038/s41588-021-00946-4

Source: https://www.nature.com/articles/s41588-021-00946-4

期刊信息

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：25.455

官方网址：https://www.nature.com/ng/

投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex