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Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration

Diabetes mellitus (DM) is a complex metabolic disorder. Long-term hyperglycemia may induce diabetic keratopathy (DK), which is mainly characterized by delayed corneal epithelial regeneration. MicroRNAs (miRNAs) have been reported to play regulatory roles during tissue regeneration. However, the mole...

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Autores principales: Zhang, Yuan, Dou, Shengqian, Qi, Xia, Zhang, Zhenzhen, Qiao, Yujie, Wang, Yani, Xie, Jin, Jiang, Hui, Zhang, Bin, Zhou, Qingjun, Wang, Qun, Xie, Lixin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427436/
https://www.ncbi.nlm.nih.gov/pubmed/34513931
http://dx.doi.org/10.3389/fmolb.2021.737472
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author Zhang, Yuan
Dou, Shengqian
Qi, Xia
Zhang, Zhenzhen
Qiao, Yujie
Wang, Yani
Xie, Jin
Jiang, Hui
Zhang, Bin
Zhou, Qingjun
Wang, Qun
Xie, Lixin
author_facet Zhang, Yuan
Dou, Shengqian
Qi, Xia
Zhang, Zhenzhen
Qiao, Yujie
Wang, Yani
Xie, Jin
Jiang, Hui
Zhang, Bin
Zhou, Qingjun
Wang, Qun
Xie, Lixin
author_sort Zhang, Yuan
collection PubMed
description Diabetes mellitus (DM) is a complex metabolic disorder. Long-term hyperglycemia may induce diabetic keratopathy (DK), which is mainly characterized by delayed corneal epithelial regeneration. MicroRNAs (miRNAs) have been reported to play regulatory roles during tissue regeneration. However, the molecular mechanism by which miRNAs influence epithelial regeneration in DK is largely unknown. In this study, we performed miRNA and mRNA sequencing of regenerative corneal epithelium tissue from streptozotocin-induced type 1 diabetic (T1DM) and wild-type mice to screen for differentially expressed miRNAs and mRNAs. Based on regulatory network analysis, miR-223-5p was selected for subsequent experiments and Hpgds was then identified as a direct target gene. MiR-223-5p downregulation significantly promoted diabetic corneal epithelial wound healing and nerve regeneration. However, the beneficial effects of miR-223-5p inhibition were abolished by an Hpgds inhibitor. Furthermore, mechanistic studies demonstrated that miR-223-5p suppression ameliorated inflammation and enhanced cell proliferation signaling in DK. Taken together, our findings revealed that the regulatory role of miR-223-5p in diabetic corneal epithelial and nerve regeneration by mediating inflammatory processes and cell proliferation signaling. And silencing miR-223-5p may contribute to the development of potential therapeutic strategies for DK.
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spelling pubmed-84274362021-09-10 Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration Zhang, Yuan Dou, Shengqian Qi, Xia Zhang, Zhenzhen Qiao, Yujie Wang, Yani Xie, Jin Jiang, Hui Zhang, Bin Zhou, Qingjun Wang, Qun Xie, Lixin Front Mol Biosci Molecular Biosciences Diabetes mellitus (DM) is a complex metabolic disorder. Long-term hyperglycemia may induce diabetic keratopathy (DK), which is mainly characterized by delayed corneal epithelial regeneration. MicroRNAs (miRNAs) have been reported to play regulatory roles during tissue regeneration. However, the molecular mechanism by which miRNAs influence epithelial regeneration in DK is largely unknown. In this study, we performed miRNA and mRNA sequencing of regenerative corneal epithelium tissue from streptozotocin-induced type 1 diabetic (T1DM) and wild-type mice to screen for differentially expressed miRNAs and mRNAs. Based on regulatory network analysis, miR-223-5p was selected for subsequent experiments and Hpgds was then identified as a direct target gene. MiR-223-5p downregulation significantly promoted diabetic corneal epithelial wound healing and nerve regeneration. However, the beneficial effects of miR-223-5p inhibition were abolished by an Hpgds inhibitor. Furthermore, mechanistic studies demonstrated that miR-223-5p suppression ameliorated inflammation and enhanced cell proliferation signaling in DK. Taken together, our findings revealed that the regulatory role of miR-223-5p in diabetic corneal epithelial and nerve regeneration by mediating inflammatory processes and cell proliferation signaling. And silencing miR-223-5p may contribute to the development of potential therapeutic strategies for DK. Frontiers Media S.A. 2021-08-26 /pmc/articles/PMC8427436/ /pubmed/34513931 http://dx.doi.org/10.3389/fmolb.2021.737472 Text en Copyright © 2021 Zhang, Dou, Qi, Zhang, Qiao, Wang, Xie, Jiang, Zhang, Zhou, Wang and Xie. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Zhang, Yuan
Dou, Shengqian
Qi, Xia
Zhang, Zhenzhen
Qiao, Yujie
Wang, Yani
Xie, Jin
Jiang, Hui
Zhang, Bin
Zhou, Qingjun
Wang, Qun
Xie, Lixin
Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration
title Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration
title_full Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration
title_fullStr Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration
title_full_unstemmed Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration
title_short Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration
title_sort transcriptional network analysis reveals the role of mir-223-5p during diabetic corneal epithelial regeneration
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427436/
https://www.ncbi.nlm.nih.gov/pubmed/34513931
http://dx.doi.org/10.3389/fmolb.2021.737472
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