作者
Sofia Ferreira-Gonzalez, Wei-Yu Lu, Alexander Raven, Benjamin Dwyer, Tak Yung Man, Eoghan O’Duibhir, Philip J Starkey Lewis, Lara Campana, Tim J Kendall, Thomas G Bird, Nuria Tarrats, Juan-Carlos Acosta, Luke Boulter, Stuart J Forbes
发表日期
2018/3/9
期刊
Nature Communications
卷号
9
期号
1
页码范围
1020
出版商
Nature Publishing Group UK
简介
Cellular senescence is a mechanism that provides an irreversible barrier to cell cycle progression to prevent undesired proliferation. However, under pathological circumstances, senescence can adversely affect organ function, viability and regeneration. We have developed a mouse model of biliary senescence, based on the conditional deletion of Mdm2 in bile ducts under the control of the Krt19 promoter, that exhibits features of biliary disease. Here we report that senescent cholangiocytes induce profound alterations in the cellular and signalling microenvironment, with recruitment of myofibroblasts and macrophages causing collagen deposition, TGFβ production and induction of senescence in surrounding cholangiocytes and hepatocytes. Finally, we study how inhibition of TGFβ-signalling disrupts the transmission of senescence and restores liver function. We identify cellular senescence as a detrimental …
学术搜索中的文章
S Ferreira-Gonzalez, WY Lu, A Raven, B Dwyer… - Nature Communications, 2018