2. Academic Validation
  3. 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

  • FASEB J. 2023 Feb;37(2):e22783. doi: 10.1096/fj.202201187RR.
Jing Li 1 2,  Jingjing Yu 1,  Weikang Huang 1,  Fan Sang 1,  Junmin Li 1,  Yanzhu Ren 2,  Huili Huang 1,  Mingli Wang 1,  Kejia Li 1,  Jun Zhang 1,  Hui Li 1,  Xiukun Cui 1,  Jing Zhang 1,  Mengyue Hu 1,  Fengling Yuan 1,  Weikai Guo 1,  Fengyan Zhang 3,  Hongmei Mu 2,  Yanzhong Hu 1 2 3
Affiliations

Affiliations

  • 1 Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan University, Kaifeng, China.
  • 2 Kaifeng Key Lab for Cataract and Myopia, Institute of Eye Disease, Kaifeng Central Hospital, Kaifeng, China.
  • 3 Department of ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
PMID: 36705056 DOI: 10.1096/fj.202201187RR
Abstract

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.

Keywords

HSP90; LRP1; PROX1; differentiation; lens epithelial cells; secretion.

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