Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou 510260, China.
Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China.
Int J Mol Sci. 2024 Sep 26;25(19):10352. doi: 10.3390/ijms251910352.
Pharmacogenomic analysis based on drug transcriptome characteristics is widely used to identify mechanisms of action. The purpose of this study was to elucidate the molecular mechanism of protective effect against adriamycin (ADM)-induced mpc5 cell injury of Chinese cordyceps aqueous extracts (WCCs) by a systematic transcriptomic analysis. The phytochemicals of WCCs were analyzed via the "phenol-sulfuric acid method", high-performance liquid chromatography (HPLC), and HPLC-mass spectrometry (MS). We analyzed the drug-reaction transcriptome profiles of mpc5 cell after treating them with WCCs. RNA-seq analysis revealed that WCCs alleviated ADM-induced mpc5 cell injury via restoring the expression of certain genes to normal level mainly in the one-carbon pool by the folate pathway, followed by the relaxin, apelin, PI3K-Akt, and nucleotide-binding, oligomerization domain (NOD)-like receptor signaling pathway, enhancing DNA synthesis and repair, cell proliferation, fibrosis reduction, and immune regulation. Otherwise, WCCs also modulated the proliferation and survival of the mpc5 cell by regulating metabolic pathways, and partially restores the expression of genes related to human disease pathways. These findings provide an innovative understanding of the molecular mechanism of the protective effect of WCCs on ADM-induced mpc5 cell injury at the molecular transcription level, and , , , , , and , etc., may be potential novel targets for treating nephrotic syndrome.
基于药物转录组特征的药物基因组学分析被广泛用于识别作用机制。本研究旨在通过系统的转录组分析阐明中国虫草水提取物(WCCs)对阿霉素(ADM)诱导的 mpc5 细胞损伤的保护作用的分子机制。通过“苯酚-硫酸法”、高效液相色谱(HPLC)和高效液相色谱-质谱(MS)分析 WCCs 的植物化学成分。我们分析了 WCCs 处理后的 mpc5 细胞的药物反应转录组谱。RNA-seq 分析表明,WCCs 通过恢复某些基因的表达至正常水平,主要是叶酸途径中的一碳池,其次是松弛素、阿片素、PI3K-Akt 和核苷酸结合寡聚化结构域(NOD)样受体信号通路,增强 DNA 合成和修复、细胞增殖、减少纤维化和免疫调节,从而减轻 ADM 诱导的 mpc5 细胞损伤。此外,WCCs 还通过调节代谢途径来调节 mpc5 细胞的增殖和存活,并部分恢复与人类疾病途径相关的基因的表达。这些发现为 WCCs 在分子转录水平上对 ADM 诱导的 mpc5 细胞损伤的保护作用的分子机制提供了创新性的认识,[化合物]等可能是治疗肾病综合征的潜在新靶点。