Heat shock factor 4 regulates lens epithelial cell homeostasis by working with lysosome and anti-apoptosis pathways
Heat shock factor 4 regulates lens epithelial cell homeostasis by working with lysosome and anti-apoptosis pathways
复制标题
热休克因子 4 通过与溶酶体和抗凋亡途径一起调节晶状体上皮细胞稳态。
DOI：
10.1016/j.biocel.2016.08.022
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发表时间：
2016-10-01
影响因子：
4
通讯作者：
Hu, Yanzhong
中科院分区：
文献类型：
--
作者：
Cui, Xiukun;Liu, Huiyuan;Hu, Yanzhong
热休克因子4介导的热休克反应的激活与出生后透镜的发育密切相关。HSF 4控制透镜上皮细胞中小的热休克蛋白（例如HSP 25和HSPAB）的表达。然而，它们在调节透镜上皮细胞稳态中的作用仍不清楚。在本文中，我们发现HSF 4在小鼠透镜上皮和纤维组织中发育性表达。HSF 4和α B-晶状体蛋白可通过稳定线粒体膜电位（Delta Y-m）和减少ROS产生，选择性地保护透镜上皮细胞免受顺铂和H2 O2诱导的凋亡。此外，令我们惊讶的是，HSF 4参与上调溶酶体活性。我们发现，与mLEC/Hsf 4-/-细胞相比，mLEC/HA-Hsf 4细胞具有增加的DLAD表达、溶酶体酸度、组织蛋白酶B活性以及质粒DNA和GFP-LC 3蛋白的降解。敲低mLECIHA-Hsf 4细胞中的Cryab抑制HSF 4介导的溶酶体酸化，而过表达Cryab可上调mLEC/Hsf 4-/-细胞中的组织蛋白酶B活性。CRAYAB可与H+泵液泡ATP酶的A亚基ATP 6V 1/A相互作用，并在溶酶体中共定位于lamp 1和lamp 2。总的来说，这些结果表明，除了调节抗凋亡，HSF 4能够通过至少控制α B-晶状体蛋白表达来调节溶酶体活性，揭示了HSF 4在调节透镜上皮细胞稳态中的新分子机制。(C)2016爱思唯尔有限公司版权所有
Activation of Heat shock factor 4-mediated heat shock response is closely associated with postnatal lens development. HSF4 controls the expression of small heat shock proteins (e.g. HSP25 and CRYAB) in lens epithelial cells. However, their roles in modulating lens epithelium homeostasis remain unclear. In this paper, we find that HSF4 is developmentally expressed in mouse lens epithelium and fiber tissue. HSF4 and alpha B-crystallin can selectively protect lens epithelial cells from cisplatin and H2O2 induced apoptosis by stabilizing mitochondrial membrane potential (Delta Y-m) and reducing ROS production. In addition, to our surprise, HSF4 is involved in upregulating lysosome activity. We found mLEC/HA-Hsf4 cells to have increased DLAD expression, lysosome acidity, cathepsin B activity, and degradation of plasmid DNA and GFP-LC3 protein when compared to mLEC/Hsf4-/- cells. Knocking down Cryab from mLECIHA-Hsf4 cells inhibits HSF4-mediated lysosome acidification, while overexpression of CRYAB can upregulate cathepsin B activity in mLEC/Hsf4-/- cells. CRAYAB can interact with ATP6V1/A the A subunit of the H+ pump vacuolar ATPase, and is colocalized to lamp1 and lamp2 in the lysosome. Collectively, these results suggest that in addition to modulating anti-apoptosis, HSF4 is able to regulate lysosome activity by at least controlling alpha B-crystallin expression, shedding light on a novel molecular mechanism of HSF4 in regulating lens epithelial cell homeostasis. (C) 2016 Elsevier Ltd. All rights reserved.