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

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 re...

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Autores principales: Cui, Yilei, Yang, Hao, Shi, Silu, Ping, Xiyuan, Zheng, Sifan, Tang, Xiajing, Yu, Xiaoning, Shentu, Xingchao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368444/
https://www.ncbi.nlm.nih.gov/pubmed/35954230
http://dx.doi.org/10.3390/cells11152385
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author Cui, Yilei
Yang, Hao
Shi, Silu
Ping, Xiyuan
Zheng, Sifan
Tang, Xiajing
Yu, Xiaoning
Shentu, Xingchao
author_facet Cui, Yilei
Yang, Hao
Shi, Silu
Ping, Xiyuan
Zheng, Sifan
Tang, Xiajing
Yu, Xiaoning
Shentu, Xingchao
author_sort Cui, Yilei
collection PubMed
description 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.
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spelling pubmed-93684442022-08-12 TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development Cui, Yilei Yang, Hao Shi, Silu Ping, Xiyuan Zheng, Sifan Tang, Xiajing Yu, Xiaoning Shentu, Xingchao Cells Article 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. MDPI 2022-08-02 /pmc/articles/PMC9368444/ /pubmed/35954230 http://dx.doi.org/10.3390/cells11152385 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cui, Yilei
Yang, Hao
Shi, Silu
Ping, Xiyuan
Zheng, Sifan
Tang, Xiajing
Yu, Xiaoning
Shentu, Xingchao
TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development
title TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development
title_full TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development
title_fullStr TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development
title_full_unstemmed TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development
title_short TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development
title_sort tp53inp2 contributes to tgf-β2-induced autophagy during the epithelial–mesenchymal transition in posterior capsular opacification development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368444/
https://www.ncbi.nlm.nih.gov/pubmed/35954230
http://dx.doi.org/10.3390/cells11152385
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