An integrated transcriptomics and network pharmacology approach to exploring the mechanism of adriamycin-induced kidney injury. (1st July 2020)

• Record Type: Journal Article
• Authors: He, Shengsheng; Li, Aiping; Zhang, Wangning; Zhang, Lichao; Liu, Yuetao; Li, Ke; Qin, Xuemei
• Is Part Of: Chemico-biological interactions. Volume 325(2020)
• Publication Date: 2020-07-01
• Subjects: Adriamycin nephropathy model -- Mechanism -- Transcriptomics -- Network pharmacology -- RT-qPCR; AN Adriamycin Nephropathy Model -- TCM Traditional Chinese Medicine -- RT-qPCR Real-Time Quantitative PCR -- DEGs Differentially Expressed Genes -- ADR Adriamycin -- NS Nephrotic Syndrome -- RNA-Seq RNA Sequencing Technology -- MPC5 Mouse Podocyte Cell line 5 -- FBS Fetal Bovine Serum -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide -- DMSO Dimethyl Sulphoxide -- TP Total Protein -- TCHO Total Cholesterol -- ALB Serum Albumin -- TG Total Triglycerides -- BUN Serum Urea Nitrogen -- Scr Serum Creatinine -- HE Hematoxylin-Eosin -- PI Propidium Iodide -- PMSF Phenylmethylsulphonyl Fluoride -- TBST Tris-Buffered Saline Tween-20 -- PVDF Polyvinylidene Fluoride -- PBS Phosphate Buffer -- VLDL Very Low Density Lipoprotein -- LDL Low Density Lipoprotein -- SD Standard Deviation; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2020.109096
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Background and aims: Adriamycin nephropathy model (AN), a rodent model of nephrotic syndrome disease that was caused by the nephrotoxicity of adriamycin, has been widely used for pharmacodynamic evaluation of traditional Chinese medicine (TCM) in the treatment of kidney injury. Although some studies have clearly shown the pathological process of AN, the mechanism of kidney injury have not been systematically investigated. Methods: The reliability of AN was evaluated by weight, urinary protein quantitation, serum biochemical and histopathological examination. Transcriptomic sequencing combined with network pharmacology were used to elucidate the molecular mechanism of AN, and cell experiment combined with real-time quantitative PCR (RT-qPCR) and was used to validate the accuracy of transcriptomic sequencing result and KEGG pathways. Results: Network analysis result showed that Mapk10 and Ptgs2 played important roles in the development of adriamycin-induced kidney injury. KEGG pathway analysis showed that the mechanism of kidney injury may be related to the regulation of biosynthesis of unsaturated fatty acids, complement and coagulation cascades, PPAR signaling pathway and PI3K-AKT signaling pathway. Conclusion: These results provide a new insight into the deep research on the mechanism of kidney injury, and provide an experimental basis for finding drug targets for the treatment of AN. Graphical abstract: Image 1 Highlights: Adriamycin nephrotic rat model can imitate human nephrotic syndrome. A value based on topological parameters is to evaluate the importance of target. The key target genes of adriamycin induced renal injury are Mapk10 and Ptgs2. Regulation of biosynthesis of unsaturated fatty acids is involved in kidney injury.