Endoplasmic reticulum Ca2+ depletion activates XBP1 and controls terminal differentiation in keratinocytes and epidermis.
Endoplasmic reticulum Ca2+ depletion activates XBP1 and controls terminal differentiation in keratinocytes and epidermis.
复制标题
DOI：
10.1111/j.1365-2133.2010.10046.x
复制
发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Mauro TM
中科院分区：
文献类型：
--
作者：
Celli A;Mackenzie DS;Crumrine DS;Tu CL;Hupe M;Bikle DD;Elias PM;Mauro TM
内质网（ER）Ca2+耗竭，以前被证明是病理性应激反应的信号，最近被发现也触发稳态生理过程，如分化。在角质形成细胞和表皮中，终末分化和屏障修复需要生理性细胞凋亡和分化，如蛋白质合成、半胱天冬酶14表达、脂质分泌和角质层（SC）形成所证明的。探讨钙耗竭诱导的内质网应激在体内和体外培养的角质形成细胞分化和屏障修复中的作用。SERCA 2 Ca 2+泵抑制剂毒胡萝卜素（TG）用于耗尽培养的角化细胞和小鼠中的ER钙。在TG处理和屏障消除后，比较ER应激因子XBP1、兜甲蛋白、半胱天冬酶14、脂质合成和细胞内Ca 2+的水平。我们在这里表明，这些组件的终末分化和屏障修复的信号生理ER应激，通过释放的颗粒层（SG）ER Ca2+商店。我们首先发现角质形成细胞和表皮ER Ca 2+耗竭激活ER应激诱导的转录因子XBP1。接下来，我们证明了外部屏障扰动导致细胞内Ca2+排空和XBP1激活。最后，我们表明，TG治疗完整的皮肤不扰乱渗透性屏障，但刺激和模仿屏障恢复的生理过程。该报告是第一份量化和定位屏障扰动后ER Ca 2+损失的报告，并表明恢复体内屏障功能的稳态过程可以仅通过诱导生理性ER应激释放ER Ca 2+来重现。
Endoplasmic reticulum (ER) Ca2+ depletion, previously shown to signal pathologic stress responses, has more recently been found also to trigger homeostatic physiologic processes such as differentiation. In keratinocytes and epidermis, terminal differentiation and barrier repair require physiologic apoptosis and differentiation, as evidenced by protein synthesis, caspase 14 expression, lipid secretion, and stratum corneum (SC) formation. To investigate the role of Ca2+ depletion induced ER stress in Keratinocytes differentiation and barrier repair in vivo and in cell culture. The SERCA2 Ca2+ pump inhibitor Thapsigargin (TG) is used to deplete ER Calcium both in cultured Keratinocytes and in mice. Levels of the ER stress factor XBP1, loricrin, Caspase 14, lipid synthesis and intracellular Ca2+ are compared after both TG treatment and barrier abrogation. We show here that these components of terminal differentiation and barrier repair are signaled by physiologic ER stress, via release of Stratum Granulosum (SG) ER Ca2+ stores. We first find that keratinocyte and epidermal ER Ca2+ depletion activate the ER-stress-induced transcription factor XBP1. Next, we demonstrate that external barrier perturbation results in both intracellular Ca2+ emptying and XBP1 activation. Finally, we show that TG treatment of intact skin does not perturb the permeability barrier, yet stimulates and mimics the physiologic processes of barrier recovery. This report is the first to quantify and localize ER Ca2+ loss after barrier perturbation and show that homeostatic processes that restore barrier function in vivo can be reproduced solely by releasing ER Ca2+, via induction of physiologic ER stress.
登录
查看更多内容
影响因子：
6
作者：
Demerjian, Marianne;Hachem, Jean-Pierre;Feingold, Kenneth R.
通讯作者：
Feingold, Kenneth R.
影响因子：
3.7
作者：
JONES, KT;SHARPE, GR
通讯作者：
SHARPE, GR
影响因子：
4.1
作者：
Ohata, Y;Hashimoto, T;Nishikawa, T
通讯作者：
Nishikawa, T
影响因子：
4
作者：
Foggia, L;Aronchik, I;Mauro, TM
通讯作者：
Mauro, TM
影响因子：
3.4
作者：
Celli, A.;Sanchez, S.;Mauro, T.
通讯作者：
Mauro, T.