转录组分析揭示 2 型糖尿病大鼠糖尿病性白内障相关的关键通路及基因
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1.中国医学科学院北京协和医学院;2.国家卫生健康委科学技术研究所;3.牡丹江医科大学

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国家自然科学基金[No.82271070];北京市自然科学基金[No.7242101];中央研究院公益基金[No.2022GJZ02]。


Transcriptomic Profiling Reveals Key Pathways and Genes Associated with Diabetic Cataract in Type 2 Diabetic Rats
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Affiliation:

1.Chinese Academy of Medical Sciences &2.Peking Union Medical College;3.Chinese Academy of Medical Sciences & Peking Union Medical College;4.amp;5.national research institute for family planning;6.Mudanjiang medical university;7.National research institute for family planning

Fund Project:

National Natural Science Foundation of China[No.82271070]; Beijing Natural Science Foundation[No.7242101]; Non-profit Central Research Institute Fund of National Research Institute For Family Planning[No.2022GJZ02]。

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    摘要:

    目的 探讨 2 型糖尿病(T2DM)大鼠晶状体前囊膜在形态学、细胞学及转录水平的改变,揭示糖尿病性白内障(DC)的发病机制。 方法 采用高脂饮食联合链脲佐菌素(STZ)腹腔注射建立 T2DM 大鼠模型;通过裂隙灯观察大鼠晶状体形态,苏木精-伊红(H&E)染色分析晶状体前囊膜组织学变化;对晶状体前囊膜进行转录组测序筛选差异表达基因(DEGs),并采用实时定量聚合酶链反应(qRT-PCR)验证;通过GO、KEGG及基因集富集分析(GSEA)探究 DEGs 的功能及相关信号通路。 结果 裂隙灯观察显示,T2DM 大鼠晶状体前囊膜呈进行性混浊且伴血管异常;H&E 染色显示,T2DM 大鼠晶状体上皮细胞(LECs)排列紊乱、密度降低。转录组测序共筛选出 1691 个 DEGs(T2DM 组 vs 正常NC组),其中 701 个上调、990 个下调。GO 富集分析显示,DEGs 主要富集于 “视觉感知”“光感受器外段”“钙离子结合” 等条目;KEGG 富集分析显示,DEGs 主要富集于 “光传导”“MAPK 信号通路”“PI3K-Akt 信号通路”“cAMP 信号通路” 等通路;GSEA 显示,T2DM 大鼠视觉信号相关通路协同下调,凋亡通路上调。qRT-PCR 验证 Adgrv1、Cnga1、Cryga、Fgf9、Tlr4、Casp12 等 DEGs 的表达趋势与转录组数据一致。 结论 T2DM 大鼠晶状体前囊膜存在转录组重构,涉及视觉功能及晶状体稳态维持的关键通路,这些发现为阐明 DC 发病机制及筛选潜在生物标志物/治疗靶点提供了依据。

    Abstract:

    Objective This study aimed to investigate the pathogenesis of Diabetic cataract (DC) by characterizing the morphological, cellular, and transcriptional changes in the lens of type 2 diabetes mellitus (T2DM) rats. Methods T2DM rat model was established via high-fat diet and streptozotocin injection. Slit-lamp was employed to inspect the lens of rats, and H E for evaluating histological alterations. Transcriptome sequencing was conducted on ocular anterior capsule to identify potential genes and validated by qRT-PCR. GO, KEGG and GSEA analyses were performed to investigate the predictive functions of differentially expressed genes (DEGs) and their associated biological pathways. Results Slit-lamp microscope revealed progressive opacification and vascular abnormalities in the anterior capsule of DM rats. H E staining showed disorganized cellular architecture and reduced density of lens epithelial cells (LECs). Transcriptome sequencing identified 1,691 DEGs between DM and NC rats, including 701 upregulated and 990 downregulated genes. Function enrichment analyses indicate the most changes happened to "visual perception," "photoreceptor outer segment," and "calcium ion binding" (GO terms), as well as "phototransduction, MAPK signaling", "PI3K-Akt signaling", and "cAMP signaling pathways" (KEGG). GSEA further demonstrated coordinated downregulation in visual signal-related pathways and upregulation in the apoptosis pathway in DM rats. qRT-PCR results of DEGs related to the above predictive functions analysis (Adgrv1, Cnga1, Cryga, Fgf9, Tlr4 and Casp12) from these pathways were consistant with transcriptome data. Conclusions This study identifies transcriptional reprogramming in the ocular anterior capsule of T2DM rats invloved in multiple pathways critical for visual function and lens homeostasis. These findings clarify diabetic cataract pathogenesis and provide potential biomarkers/targets for therapeutic intervention.

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  • 收稿日期:2025-10-17
  • 最后修改日期:2026-04-17
  • 录用日期:2026-05-18
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