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

Yilei Cui; Hao Yang; Silu Shi; Xiyuan Ping; Sifan Zheng; Xiajing Tang; Xiaoning Yu; Xingchao Shentu

doi:10.3390/cells11152385

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.

Authors

Yilei Cui^{1

2}, Hao Yang^{1

2}, Silu Shi^{1

2}, Xiyuan Ping^{1

2}, Sifan Zheng³, 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy
Capsule Opacification* / metabolism
Epithelial-Mesenchymal Transition / genetics
Humans
Nuclear Proteins / metabolism*
Transforming Growth Factor beta2 / metabolism*
Tumor Suppressor Protein p53

Substances

Nuclear Proteins
TP53INP2 protein, human
Transforming Growth Factor beta2
Tumor Suppressor Protein p53

Grants and funding

This research was funded by the National Natural Science Foundation of China (Grant No. 82171033, 81970781, and 81800869) and the Natural Science Foundation of Zhejiang Province (Grant No. LD21H120001).