TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial-Mesenchymal Transition in Posterior Capsular Opacification Development

  • Cells. 2022 Aug 2;11(15):2385. doi: 10.3390/cells11152385.
Yilei Cui  1  2 ,  Hao Yang  1  2 ,  Silu Shi  1  2 ,  Xiyuan Ping  1  2 ,  Sifan Zheng  3 ,  Xiajing Tang  1  2 ,  Xiaoning Yu  1  2 ,  Xingchao Shentu  1  2
Affiliations
  • 1. Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
  • 2. Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou 310009, China.
  • 3. GKT School of Medical Education, King's College London, London WC2R 2LS, UK.
PMID: 35954230 DOI: 10.3390/cells11152385
Abstract

Background: Posterior capsule opacification (PCO) is the most common complication after cataract surgery, in which increased levels of transforming growth factor-beta 2 (TGF-β2) accelerate PCO formation; however, the pathological mechanisms are not fully understood. This study aims to explore the regulation mechanism of TGF-β2 in PCO formation via its autophagic functions.

Methods: The autophagic effect of TGF-β2 was detected by transmission electron microscopy (TEM), Western blotting, and immunofluorescence analysis. The association between Autophagy and the epithelial-mesenchymal transition (EMT) was evaluated by qPCR and Western blotting. The transcriptome analysis was used to uncover the molecular mechanism of TGF-β2-induced PCO formation.

Results: TGF-β2 specifically promotes Autophagy flux in human lens epithelial cells. The activation of Autophagy by rapamycin can promote EMT marker synthesis and improve cell migration. However, the inhibition of Autophagy by 3-MA attenuates EMT. To uncover the molecular mechanisms, we performed RNA Sequencing and found that TGF-β2 elevated tumor protein p53-inducible nuclear protein2 (TP53INP2) expression, which was accompanied by a nuclear-to-cytoplasm translocation. Moreover, the knockdown of TP53INP2 blocked the TGF-β2-induced Autophagy and EMT processes, revealing that TP53INP2 plays an important role in TGF-β2-induced Autophagy during EMT.

Conclusions: Taken together, the results of this study suggested that TP53INP2 was a novel regulator of PCO development by TGF-β2, and notably, TP53INP2, may be a potential target for the pharmacological treatment of PCO.

Keywords
TGF-β2; TP53INP2; autophagy; epithelial–mesenchymal transition; posterior capsule opacification.
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