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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| Format: | Article |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.737472/full |
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| author | Yuan Zhang Yuan Zhang Yuan Zhang Shengqian Dou Shengqian Dou Xia Qi Xia Qi Zhenzhen Zhang Zhenzhen Zhang Zhenzhen Zhang Yujie Qiao Yujie Qiao Yani Wang Yani Wang Yani Wang Jin Xie Jin Xie Hui Jiang Hui Jiang Bin Zhang Bin Zhang Qingjun Zhou Qingjun Zhou Qun Wang Qun Wang Lixin Xie Lixin Xie |
| author_facet | Yuan Zhang Yuan Zhang Yuan Zhang Shengqian Dou Shengqian Dou Xia Qi Xia Qi Zhenzhen Zhang Zhenzhen Zhang Zhenzhen Zhang Yujie Qiao Yujie Qiao Yani Wang Yani Wang Yani Wang Jin Xie Jin Xie Hui Jiang Hui Jiang Bin Zhang Bin Zhang Qingjun Zhou Qingjun Zhou Qun Wang Qun Wang Lixin Xie Lixin Xie |
| author_sort | Yuan Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T12:58:23Z |
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| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-17T12:58:23Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-d2b02461598a4fa6b726073f8e486aff2022-12-21T21:47:26ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-08-01810.3389/fmolb.2021.737472737472Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial RegenerationYuan Zhang0Yuan Zhang1Yuan Zhang2Shengqian Dou3Shengqian Dou4Xia Qi5Xia Qi6Zhenzhen Zhang7Zhenzhen Zhang8Zhenzhen Zhang9Yujie Qiao10Yujie Qiao11Yani Wang12Yani Wang13Yani Wang14Jin Xie15Jin Xie16Hui Jiang17Hui Jiang18Bin Zhang19Bin Zhang20Qingjun Zhou21Qingjun Zhou22Qun Wang23Qun Wang24Lixin Xie25Lixin Xie26State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaDepartment of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaEye Center, Renmin Hospital of Wuhan University, Wuhan, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaMedical College, Qingdao University, Qingdao, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaMedical College, Qingdao University, Qingdao, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, ChinaQingdao Eye Hospital of Shandong First Medical University, Qingdao, ChinaDiabetes 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.https://www.frontiersin.org/articles/10.3389/fmolb.2021.737472/fulldiabetic keratopathywound healinghigh-throughput sequencingmiR-223-5pHpgds |
| spellingShingle | Yuan Zhang Yuan Zhang Yuan Zhang Shengqian Dou Shengqian Dou Xia Qi Xia Qi Zhenzhen Zhang Zhenzhen Zhang Zhenzhen Zhang Yujie Qiao Yujie Qiao Yani Wang Yani Wang Yani Wang Jin Xie Jin Xie Hui Jiang Hui Jiang Bin Zhang Bin Zhang Qingjun Zhou Qingjun Zhou Qun Wang Qun Wang Lixin Xie Lixin Xie Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration Frontiers in Molecular Biosciences diabetic keratopathy wound healing high-throughput sequencing miR-223-5p Hpgds |
| 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 | diabetic keratopathy wound healing high-throughput sequencing miR-223-5p Hpgds |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.737472/full |
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