Extensive pancreas regeneration following acinar-specific disruption of Xbp1 in mice.
Extensive pancreas regeneration following acinar-specific disruption of Xbp1 in mice.
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DOI：
10.1053/j.gastro.2011.06.045
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发表时间：
2011-10
期刊：
影响因子：
29.4
通讯作者：
Konieczny SF
中科院分区：
文献类型：
--
作者：
Hess DA;Humphrey SE;Ishibashi J;Damsz B;Lee AH;Glimcher LH;Konieczny SF
胰腺外分泌疾病的进展，包括胰腺炎和癌症，与细胞应激水平的增加有关。胰腺腺泡细胞参与了这些疾病的发生发展，由于其高水平的蛋白质输出，它们需要一个有效的未折叠蛋白反应(UPR)，该反应介导错误折叠蛋白积累后内质网(ER)应激的恢复。为了研究外分泌器官从内质网应激中恢复的情况，我们在大多数成年胰腺腺泡细胞(Xbp1fl/fl)中条件中断了XBP1(UPR的一个主要成分)。我们监测了结构性内质网应激对这些小鼠外分泌胰腺的影响。XBP1缺失的腺泡细胞经历了广泛的凋亡，随后胰腺经历了一个快速的恢复期，包括中央腺泡细胞间的扩张，包含Hes1和Sox9表达细胞的管状复合体的形成，以及从剩余的XBP1+细胞群中再生表达Mist1的腺泡细胞。XBP1似乎是小鼠腺泡细胞内稳态所必需的；内质网应激诱导胰腺中涉及腺泡和中央腺泡细胞的再生反应，并促进器官从外分泌胰腺疾病中恢复。
Progression of diseases of the exocrine pancreas, which include pancreatitis and cancer, is associated with increased levels of cell stress. Pancreatic acinar cells are involved in development of these diseases and, because of their high level of protein output, they require an efficient, unfolded protein response (UPR), which mediates recovery from endoplasmic reticulum (ER) stress following the accumulation of misfolded proteins. To study recovery from ER stress in the exocrine organ, we generated mice with conditional disruption of Xbp1 (a principle component of the UPR) in most adult pancreatic acinar cells (Xbp1fl/fl). We monitored the effects of constitutive ER stress in the exocrine pancreas of these mice. Xbp1-null acinar cells underwent extensive apoptosis, followed by a rapid phase of recovery in the pancreas that included expansion of the centroacinar cell compartment, formation of tubular complexes that contained Hes1- and Sox9-expressing cells, and regeneration of acinar cells that expressed Mist1 from the residual, surviving Xbp1+ cell population. XBP1 appears to be required for homeostatisis of acinar cells in mice; ER stress induces a regenerative response in the pancreas that involves acinar and centroacinar cells and promotes organ recovery from exocrine pancreas disease.
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DOI：
10.1084/jem.20090738
发表时间：
2009-09-28
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Todd DJ;McHeyzer-Williams LJ;Kowal C;Lee AH;Volpe BT;Diamond B;McHeyzer-Williams MG;Glimcher LH
通讯作者：
Glimcher LH
影响因子：
64.8
作者：
Reimold, AM;Iwakoshi, NN;Glimcher, LH
通讯作者：
Glimcher, LH
DOI：
10.1073/pnas.0912589107
发表时间：
2010-01-05
影响因子：
11.1
作者：
Rovira, Meritxell;Scott, Sherri-Gae;Leach, Steven D.
通讯作者：
Leach, Steven D.
影响因子：
11.4
作者：
Lee, AH;Chu, GC;Glimcher, LH
通讯作者：
Glimcher, LH
影响因子：
29.4
作者：
Strobel, Oliver;Dor, Yuval;Thayer, Sarah P.
通讯作者：
Thayer, Sarah P.