title: Analysis of the gene expression profile of curcumin-treated kidney on endotoxin-induced renal inflammation.
abstract: Acute or chronic kidney inflammation is closely related to the progress of kidney diseases. Curcumin, a yellow pigment present in the rhizome of turmeric (Curcuma longa L. Zingiberaceae), was found to be a potential anti-inflammatory agent. The present study aimed to investigate the effects and explore the protective mechanism of curcumin on lipopolysaccharide (LPS)-induced kidney inflammation in mice using gene chip and pathological technology. Nine SPF Kunming mice (aged 6-8 weeks, weighing 20-25 g) were divided into three groups. Saline and LPS were injected intraperitoneally in a normal control group and a model group, respectively. Mice in the treatment group were first injected with curcumin (5 mg/kg) for 3 days before being injected with LPS (5 mg/kg). Kidney tissues were harvested at 6 h after treatment. Parts of kidney were fixed with 10 % formaldehyde for HE, Periodic acid-Schiff staining, and immunohistochemistry. Affymetrix gene chips (mouse 430 chip) were used to detect the renal gene expression profile, and the results were analyzed using bioinformatics methods. The renal gene expression profile showed that there are 148 Affy IDs (up-down group) whose levels of gene expression were increased after LPS stimulation and decreased by curcumin treatment and that there are 133 Affy IDs (down-up group) exhibiting the opposite trend. In the differentially expressed genes of the up-down group, 21 Gene Ontology (GO) genes were selected by screening function (P ≤ 0.01). In the biological processes, most of the genes were found to be related to the genes of regulation of macrophage activation and macrophage activation-associated genes. In the cellular localization, there were four functional GO genes (P ≤ 0.01); in the molecular structure, there were seven functional GO genes (P ≤ 0.01). In the down-up group, there were functional GO genes (P ≤ 0.01) and one functional GO gene (P ≤ 0.01) in the biological process and the cellular localization, respectively. Macrophage infiltration could be observed as early as 6 h after LPS stimulation. Pretreatment with 5 mg/kg of curcumin significantly decreased the macrophage infiltration. At 6 h after LPS injection, significant decreased expression of M6PRBP-1 and NEDD-4 was observed in renal tissue. On the other hand, pretreatment with curcumin significantly increased renal M6PRBP-1 and NEDD-4 expression. In this study, we also found the signaling pathway and the possible target gene of the protective effects of curcumin on endotoxin-induced renal inflammation. The kidney gene expression profile in the inflammatory state was clarified by using gene chip technology. Furthermore, we confirmed that curcumin treatment can change the gene expression profile.
authors.affiliation: Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhong
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Yuanmeng
authors.initials: Y
authors.lastname: Jin
authors.forename: Shanmai
authors.initials: S
authors.lastname: Guo
authors.forename: Weiming
authors.initials: W
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis; D003474:Curcumin / Q000494:pharmacology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000096:biosynthesis; D015870:Gene Expression; D020869:Gene Expression Profiling; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D000075702:Nedd4 Ubiquitin Protein Ligases; D009393:Nephritis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D000070796:Perilipin-3; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D008070:Lipopolysaccharides; D000070796:Perilipin-3; C523440:Plin3 protein, mouse; D000075702:Nedd4 Ubiquitin Protein Ligases; D044767:Ubiquitin-Protein Ligases; D003474:Curcumin