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通过高通量测序和生物信息学分析鉴定干细胞治疗2型糖尿病诱导的勃起功能障碍大鼠中的关键基因。

Identification of key genes in type 2 diabetes-induced erectile dysfunction rats with stem cell therapy through high-throughput sequencing and bioinformatic analysis.

作者信息

Kang Jia-Qi, Song Yu-Xuan, Liu Li, Lu Yi, Tian Jia, Hu Rui, Wang Xiao, Liu Xiao-Qiang

机构信息

Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.

出版信息

Andrologia. 2021 Jun;53(5):e14031. doi: 10.1111/and.14031. Epub 2021 Mar 23.

Abstract

Diabetes mellitus erectile dysfunction (DMED) is a frequent complication of diabetes. Mesenchymal stem cell (MSC) therapy was demonstrated to improve erectile function in DMED. However, the pathogenesis of DMED and the mechanism by which MSCs function are still unclear. We established a rat model of DMED and gave MSC therapy through intracavernous injection. After transcriptome sequencing of rats' penile tissue, we identified a total of 1,097 overlapped differentially expressed genes (DEGs) of the normal control group, DMED group, and MSC-treated group, containing 189 upregulated genes and 908 downregulated genes. The enriched functions of upregulated DEGs included extracellular matrix organisation (GO:0030198), extracellular structure organisation (GO:0043062), and wound healing (GO:0042060), PPAR signalling pathway (rno03320), arachidonic acid metabolism (rno00590) and retinol metabolism (rno00830). The enriched functions of downregulated DEGs included peptidase activity (GO:0052547), hair follicle development (GO:0001942), intermediate filament-based process (GO:0045103), nitrogen metabolism (rno00910), aldosterone-regulated sodium reabsorption (rno04960) and retinol metabolism (rno00830). We constructed a PPI network with 547 nodes and 2,365 edges and identified 15 hub genes with high connectivity degree. In summary, 15 hub genes with potential roles in the development of ED were identified. Further functional research would be required to elucidate the molecular mechanism underlying misregulated genes.

摘要

糖尿病性勃起功能障碍(DMED)是糖尿病常见的并发症。间充质干细胞(MSC)疗法已被证明可改善DMED患者的勃起功能。然而,DMED的发病机制以及MSC发挥作用的机制仍不清楚。我们建立了DMED大鼠模型,并通过海绵体内注射给予MSC治疗。对大鼠阴茎组织进行转录组测序后,我们共鉴定出正常对照组、DMED组和MSC治疗组的1097个重叠差异表达基因(DEG),其中包括189个上调基因和908个下调基因。上调DEG的富集功能包括细胞外基质组织(GO:0030198)、细胞外结构组织(GO:0043062)和伤口愈合(GO:0042060)、PPAR信号通路(rno03320)、花生四烯酸代谢(rno00590)和视黄醇代谢(rno00830)。下调DEG的富集功能包括肽酶活性(GO:0052547)、毛囊发育(GO:0001942)、基于中间丝的过程(GO:0045103)、氮代谢(rno00910)、醛固酮调节的钠重吸收(rno04960)和视黄醇代谢(rno00830)。我们构建了一个包含547个节点和2365条边的蛋白质-蛋白质相互作用(PPI)网络,并鉴定出15个具有高连接度的枢纽基因。总之,我们鉴定出15个在勃起功能障碍发展中可能起作用的枢纽基因。需要进一步的功能研究来阐明基因调控异常背后的分子机制。

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