Xu Feng, Gao Feng
Department of Spine Surgery. the First Hospital of Jilin University Department of Orthopedic, the Second Hospital of Jilin University, Changchun, Jilin Province, China.
Medicine (Baltimore). 2018 Aug;97(31):e11659. doi: 10.1097/MD.0000000000011659.
This study aimed to investigate the potential therapeutic targets of Liuwei Dihuang pill (LDP) in the treatment of postmenopausal osteoporosis with kidney-Yin deficiency (PMO-KY).Gene expression data were downloaded from the GEO database, including 4 PMO-KY samples and 3 healthy postmenopausal controls from GSE56116, as well as 3 PMO-KY samples before LDP treatment and 3 PMO-KY samples after three months of LDP treatment from GSE57273. Limma package was used to identify differentially expressed genes (DEGs). Afterwards, the potential target genes of LDP (namely key DEGs) were identified according to the comparison of DEGs in PMO-KY group and the DEGs in LDP treatment groups. Subsequently, iRegulon plugin in Cytoscape software was used to predict potential transcription factors (TFs) that regulated the key DEGs, and Comparative Toxicogenomics Database was utilized to identify known PMO-related genes among the key DEGs.Totally, 202 and 2066 DEGs were identified between PMO-KY and controls, as well as after-treatment and before-treatment groups, respectively. Among them, 52 DEGs were up-regulated in PMO-KY but down-regulated after LDP treatment, and 8 TFs were predicted to these DEGs. Furthermore, 34 DEGs were down-regulated in PMO-KY but up-regulated after treatment, and 7 TFs were predicted to regulate these DEGs. Additionally, 43 of the 86 key DEGs were known PMO-related genes.NCOA3, TCF4, DUSP6, PELI2, and STX7 were predicted to be regulated by HOXA13. In the PMO-KY treatment, NCOA3, TCF4, DUSP6, PELI2, and STX7 might be the potential therapeutic targets of LDP. However, further investigation is required to confirm these genes.
本研究旨在探讨六味地黄丸(LDP)治疗肾阴虚型绝经后骨质疏松症(PMO-KY)的潜在治疗靶点。基因表达数据从GEO数据库下载,包括来自GSE56116的4个PMO-KY样本和3个健康绝经后对照,以及来自GSE57273的3个LDP治疗前的PMO-KY样本和3个LDP治疗三个月后的PMO-KY样本。使用Limma软件包鉴定差异表达基因(DEG)。之后,根据PMO-KY组中的DEG与LDP治疗组中的DEG的比较,鉴定LDP的潜在靶基因(即关键DEG)。随后,使用Cytoscape软件中的iRegulon插件预测调节关键DEG的潜在转录因子(TF),并利用比较毒理基因组学数据库在关键DEG中鉴定已知的PMO相关基因。在PMO-KY与对照组之间以及治疗后与治疗前组之间,分别共鉴定出202个和2066个DEG。其中,52个DEG在PMO-KY中上调但在LDP治疗后下调,并且预测有8个TF作用于这些DEG。此外,34个DEG在PMO-KY中下调但在治疗后上调,并且预测有7个TF调节这些DEG。另外,86个关键DEG中有43个是已知的PMO相关基因。预测NCOA3、TCF4、DUSP6、PELI2和STX7受HOXA13调节。在PMO-KY治疗中,NCOA3、TCF4、DUSP6、PELI2和STX7可能是LDP的潜在治疗靶点。然而,需要进一步研究来证实这些基因。