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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9368444 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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