Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration.
Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration.
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转录网络分析揭示 miR-223-5p 在糖尿病角膜上皮再生过程中的作用
DOI：
10.3389/fmolb.2021.737472
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发表时间：
2021
影响因子：
5
通讯作者：
Xie L
中科院分区：
文献类型：
--
作者：
Zhang Y;Dou S;Qi X;Zhang Z;Qiao Y;Wang Y;Xie J;Jiang H;Zhang B;Zhou Q;Wang Q;Xie L
糖尿病（DM）是一种复杂的代谢性疾病。长期高血糖可导致以角膜上皮再生延迟为主要特征的糖尿病性角膜病变（DK）。MicroRNAs（miRNAs）在组织再生过程中起着重要的调控作用。然而，miRNAs影响DK上皮再生的分子机制在很大程度上是未知的。在这项研究中，我们对链脲佐菌素诱导的1型糖尿病（T1 DM）小鼠和野生型小鼠的再生角膜上皮组织进行了miRNA和mRNA测序，以筛选差异表达的miRNA和mRNA。基于调控网络分析，选择miR-223- 5 p用于后续实验，然后将Hpgds鉴定为直接靶基因。miR-223- 5 p下调显著促进糖尿病角膜上皮创伤愈合和神经再生。然而，miR-223- 5 p抑制的有益作用被Hpgds抑制剂消除。此外，机制研究表明，miR-223- 5 p抑制可改善DK中的炎症并增强细胞增殖信号传导。综上所述，我们的研究结果揭示了miR-223- 5 p通过介导炎症过程和细胞增殖信号在糖尿病角膜上皮和神经再生中的调节作用。沉默miR-223- 5 p可能有助于DK潜在治疗策略的开发。
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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影响因子：
4.6
作者：
Kulkarni M;Leszczynska A;Wei G;Winkler MA;Tang J;Funari VA;Deng N;Liu Z;Punj V;Deng SX;Ljubimov AV;Saghizadeh M
通讯作者：
Saghizadeh M
影响因子：
2.8
作者：
Kumar N;Pop-Busui R;Musch DC;Reed DM;Momont AC;Hussain M;Raval N;Moroi SE;Shtein R
通讯作者：
Shtein R
影响因子：
3.7
作者：
Funari VA;Winkler M;Brown J;Dimitrijevich SD;Ljubimov AV;Saghizadeh M
通讯作者：
Saghizadeh M
影响因子：
2.1
作者：
FRIEND, J;ISHII, Y;THOFT, RA
通讯作者：
THOFT, RA
影响因子：
2.7
作者：
Huang, Yongjian;Qian, Chaoxu;Xue, Jinsong
通讯作者：
Xue, Jinsong