Extracellular HSP90 promotes differentiation of lens epithelial cells to fiber cells by activating LRP1‐YAP‐PROX1 axis
Extracellular HSP90 promotes differentiation of lens epithelial cells to fiber cells by activating LRP1‐YAP‐PROX1 axis
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细胞外HSP90通过激活LRP1→YAP→PROX1轴促进晶状体上皮细胞向纤维细胞分化
DOI：
10.1096/fj.202201187rr
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发表时间：
2023-01
期刊：
影响因子：
--
通讯作者：
Yanzhong Hu
中科院分区：
文献类型：
--
作者：
Jing Li;Jingjing Yu;Weikang Huang;Fan Sang;Junmin Li;Yanzhu Ren;Huili Huang;Mingli Wang;Kejia Li;Jun Zhang;Hui Li;Xiukun Cui;Jing Zhang;Mengyue Hu;Fengling Yuan;Weikai Guo;Fengyan Zhang;Hongmei Mu;Yanzhong Hu
白内障术后残留晶状体上皮细胞向纤维细胞分化或向肌成纤维细胞分化，导致后囊混浊。潜在的监管机制仍不清楚。利用人晶状体上皮细胞株和体外培养的大鼠晶状体囊袋模型，我们发现晶状体上皮细胞通过自噬途径分泌细胞外热休克蛋白90α(EHSP90)。给予重组GST-HSP90α蛋白或其M结构域诱导大鼠CRLEC细胞的延长，伴随着关键的纤维细胞转录因子PROX1及其下游靶点β-和γ-晶体蛋白和结构蛋白的上调。这一调控被PROX1 siRNA废除。GST-HSP90AKT通过与α结合，激活LRP1-AKT介导的YAP降解，上调PROX1的表达。GST-HSP90α对PROX1表达和细胞伸长的上调可被LRP1和AKT抑制剂抑制，但被YAP-1抑制剂(VP)激活。这些结果表明，晶状体囊膜残留上皮细胞上调并分泌eHSP90α，进而推动晶状体上皮细胞向纤维细胞分化。重组热休克蛋白90α蛋白是晶状体再生过程中潜在的一种新的分化调节因子。
Capsular residual lens epithelial cells (CRLEC) undergo differentiation to fiber cells for lens regeneration or tansdifferentiation to myofibroblasts leading to posterior capsular opacification (PCO) after cataract surgery. The underlying regulatory mechanism remains unclear. Using human lens epithelial cell lines and the ex vivo cultured rat lens capsular bag model, we found that the lens epithelial cells secrete HSP90α extracellularly (eHSP90) through an autophagy‐associated pathway. Administration of recombinant GST‐HSP90α protein or its M‐domain induces the elongation of rat CRLEC cells with concomitant upregulation of the crucial fiber cell transcriptional factor PROX1and its downstream targets, β‐ and γ‐crystallins and structure proteins. This regulation is abolished by PROX1 siRNA. GST‐HSP90α upregulates PROX1 by binding to LRP1 and activating LRP1‐AKT mediated YAP degradation. The upregulation of GST‐HSP90α on PROX1 expression and CRLEC cell elongation is inhibited by LRP1 and AKT inhibitors, but activated by YAP‐1 inhibitor (VP). These data demonstrated that the capsular residue epithelial cells upregulate and secrete eHSP90α, which in turn drive the differentiation of lens epithelial cell to fiber cells. The recombinant HSP90α protein is a potential novel differentiation regulator during lens regeneration.
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DOI：
10.1016/s2352-4642(19)30150-6
发表时间：
2019-07
期刊：
The Lancet. Child & adolescent health
影响因子：
--
作者：
A. Mataftsi;A. Haidich;N. Ziakas
通讯作者：
A. Mataftsi;A. Haidich;N. Ziakas
影响因子：
3.7
作者：
Anchan RM;Lachke SA;Gerami-Naini B;Lindsey J;Ng N;Naber C;Nickerson M;Cavallesco R;Rowan S;Eaton JL;Xi Q;Maas RL
通讯作者：
Maas RL
影响因子：
0.8
作者：
I. Neuhann;Lukas Neuhann;T. Neuhann
通讯作者：
I. Neuhann;Lukas Neuhann;T. Neuhann
影响因子：
4.4
作者：
Lois, N;Dawson, R;Forrester, JV
通讯作者：
Forrester, JV
分子伴侣 Hsp90α 缺陷通过破坏光感受器中的高尔基组织和囊泡运输而导致视网膜变性
影响因子：
5.5
作者：
Yuan Wu;Xiudan Zheng;Yubo Ding;Min Zhou;Zhuang Wei;Tao Liu;Kan Liao
通讯作者：
Kan Liao