Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
J Mol Med (Berl). 2022 Nov;100(11):1569-1585. doi: 10.1007/s00109-022-02251-x. Epub 2022 Sep 12.
With the rapid increase in the incidence of diabetes, non-healing diabetic wounds have posed a huge challenge to public health. Endothelial progenitor cell (EPC) has been widely reported to promote wound repairing, while its number and function were suppressed in diabetes. However, the specific mechanisms and competing endogenous RNA (ceRNA) network of EPCs in diabetes remain largely unknown. Thus, the transcriptome analyses were carried in the present study to clarify the mechanism underlying EPCs dysfunction in diabetes. EPCs were successfully isolated from rats. Compared to the control, diabetic rat-derived EPCs displayed impaired proliferation, migration, and tube formation ability. The differentially expressed (DE) RNAs were successfully identified by RNA sequencing in the control and diabetic groups. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DE mRNAs were significantly enriched in terms and pathways involved in the functions of EPCs and wound healing. Protein-protein interaction networks revealed critical DE mRNAs in the above groups. Moreover, the whole lncRNA-miRNA-mRNA ceRNA network was constructed, in which 9 lncRNAs, 9 mRNAs, and 5 miRNAs were further validated by quantitative real-time polymerase chain reaction. Rno-miR-10b-5p and Tgfb2 were identified as key regulators of EPCs dysfunction in diabetes. The present research provided novel insight into the underlying mechanism of EPCs dysfunction in diabetes and prompted potential targets to restore the impaired functions, thus accelerating diabetic wound healing. KEY MESSAGES: • Compared to the control, diabetic rat-derived EPCs displayed impaired proliferation, migration, and tube formation ability. • The DE RNAs were successfully identified by RNA sequencing in the control and diabetic groups and analyzed by DE, GO, and KEGG analysis. • PPI and lncRNA-miRNA-mRNA ceRNA networks were constructed. • 9 lncRNAs, 9 mRNAs, and 5 miRNAs were further validated by qRT-PCR. • Rno-miR-10b-5p and Tgfb2 were identified as key regulators of EPCs dysfunction in diabetes.
随着糖尿病发病率的迅速增加，糖尿病不愈合创面给公共健康带来了巨大挑战。内皮祖细胞（EPC）已被广泛报道可促进创面修复，但其数量和功能在糖尿病中受到抑制。然而，EPC 在糖尿病中的具体机制和竞争内源性 RNA（ceRNA）网络仍知之甚少。因此，本研究进行了转录组分析，以阐明糖尿病中 EPC 功能障碍的机制。成功从大鼠中分离出 EPC。与对照组相比，糖尿病大鼠来源的 EPC 增殖、迁移和管腔形成能力受损。通过 RNA 测序成功鉴定出对照组和糖尿病组的差异表达（DE）RNA。基因本体论和京都基因与基因组百科全书分析表明，DE mRNAs 在与 EPC 功能和创面愈合相关的术语和途径中显著富集。蛋白质-蛋白质相互作用网络揭示了上述各组中关键的 DE mRNAs。此外，构建了完整的 lncRNA-miRNA-mRNA ceRNA 网络，其中 9 个 lncRNA、9 个 mRNA 和 5 个 miRNA 通过定量实时聚合酶链反应进一步验证。Rno-miR-10b-5p 和 Tgfb2 被鉴定为糖尿病中 EPC 功能障碍的关键调节因子。本研究为糖尿病中 EPC 功能障碍的潜在机制提供了新的见解，并提示了恢复受损功能的潜在靶点，从而加速糖尿病创面愈合。
与对照组相比，糖尿病大鼠来源的 EPC 增殖、迁移和管腔形成能力受损。
通过 RNA 测序成功鉴定出对照组和糖尿病组的差异表达 RNA，并通过 DE、GO 和 KEGG 分析进行分析。
构建了蛋白质-蛋白质相互作用和 lncRNA-miRNA-mRNA ceRNA 网络。
通过 qRT-PCR 进一步验证了 9 个 lncRNA、9 个 mRNA 和 5 个 miRNA。
Rno-miR-10b-5p 和 Tgfb2 被鉴定为糖尿病中 EPC 功能障碍的关键调节因子。
