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TGF-β2 increases eHSP90α secretion via upregulating secretory autophagy pathway.

Jing Li1,2, Junmin Li1, Tong Xie1

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|November 13, 2025
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Summary

Extracellular heat shock protein 90α (eHSP90α) secretion from lens epithelial cells involves secretory autophagy. Transforming growth factor-beta 2 (TGF-β2) enhances eHSP90α secretion, promoting lens cell differentiation.

Keywords:
Extracellular HSP90αSEC22BSecretory autophagyTGF-β2Unconventional protein secretion

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Ophthalmology

Background:

  • Extracellular heat shock protein 90α (eHSP90α) regulates key cellular processes including cell differentiation.
  • Lens epithelial cells secrete eHSP90α, which is crucial for lens regeneration by promoting differentiation into lens fiber cells.
  • Autophagy is implicated in eHSP90α secretion, but the precise mechanism is not fully understood.

Purpose of the Study:

  • To elucidate the mechanism of extracellular heat shock protein 90α (eHSP90α) secretion from lens epithelial cells.
  • To investigate the role of autophagy in eHSP90α secretion.
  • To determine how Transforming Growth Factor-beta 2 (TGF-β2) influences eHSP90α secretion and subsequent lens cell differentiation.

Main Methods:

  • Utilized lens epithelial cell lines, ex vivo cultured rat lens capsular bags, and primary rat lens epithelial cells.
  • Employed immunoblotting, qPCR, immunofluorescence staining, siRNA/CRISPR-Cas9 gene knockdown, ChIP assays, and nuclear/cytoplasmic extraction assays.
  • Investigated protein and mRNA expression, autophagosome formation, protein co-localization, gene silencing, transcriptional factor binding, and nuclear translocation.

Main Results:

  • Extracellular heat shock protein 90α (eHSP90α) is secreted via the secretory autophagy pathway, involving interactions with TRIM16 and SEC22B.
  • Transforming Growth Factor-beta 2 (TGF-β2) upregulates eHSP90α secretion by activating the secretory autophagy pathway through p38 and ERK1/2 signaling.
  • TGF-β2 also increases SEC22B expression via ERK1/2-mediated nuclear translocation of TFEB and TFE3, ultimately promoting lens epithelial cell differentiation.

Conclusions:

  • Lens epithelial cell secretion of eHSP90α occurs through a secretory autophagy pathway involving TRIM16 and SEC22B.
  • Transforming Growth Factor-beta 2 (TGF-β2) enhances eHSP90α secretion by upregulating the secretory autophagy pathway.
  • The TGF-β2-induced increase in eHSP90α secretion promotes lens epithelial cell differentiation into lens fiber cells.