(JNK) in cultured mesangial cells, but the functional implication of this phenomenon remains to be determined, largely due to the lack of an effective approach to block JNK. Therefore, the present study was carried out to examine whether JNK is involved in ANG II-induced cell proliferation in cultured human mesangial cells (HMCs) with the use of a newly developed JNK-selective blocker, SP-600125. Within minutes, treatment with 100 nM ANG II activated all three members of MAP kinase family, including extracellular signal-regulated protein kinase (Erk) 1/2, JNK, and p38 in cultured HMCs, as assessed by immunoblotting detection of phosphorylation of MAP kinases. ANG II-dependent activation of JNK was further confirmed by detection of increased phosphorylation and transcription activity of c-Jun after the ANG II treatment. SP-600125 ranging from 5 to 10 M almost completely abolished the activation of JNK by ANG II without affecting the activities of Erk1/2 and p38. After treatment with 100 ng ANG II, there was a steady increase in [ 3 H]thymidine incorporation that was blocked by SP-60025 in a dose-and time-dependent manner. Similarly, SP-600125 dose dependently reduced the ANG II-induced increase in cell number. The antiproliferative effect of SP-60025 was further determined by cell-cycle analysis with flow cytometry. Twenty-four hours after ANG II treatment, 50% of the quiescent HMCs (G0/G1) progressed into the S phase, and the cell cycle progression was almost completely prevented in the presence of SP-60025. Our data suggest that JNK mediates the proliferative effect of ANG II in cultured HMCs and thus represents a novel therapeutic target for treatment of chronic renal diseases. cell cycle MESANGIAL CELLS (MCS) ARE a prominent cell type located inside the glomeruli or in the extraglomerular mesangium of the juxtaglomerular apparatus and play an important role in maintenance of structural and functional integrity of the glomeruli (6, 26). MCs are considered to be derived mesenchymal cells and share similar properties with vascular smooth muscle cells (VSMCs). Like VSMCs, MCs can exhibit contractile and proliferative responses to vasoactive substances such as angiotensin II (ANG II) (39). Proliferation of MCs is almost invariably associated with various forms of glomerular renal diseases. Understanding the mechanisms governing MC proliferation may lead to the development of new therapeutic interventions for the devastating diseases.ANG II is best known for its role in the control of extracellular volume and blood pressure (12,13,28). Emerging evidence suggests that ANG II plays a role in the pathogenesis of various forms of chronic renal diseases through mediating the inflammatory responses. In this regard, angiotensin-converting enzyme inhibitors and AT 1 -receptor antagonists exhibit renal beneficial effects in both human and animals that cannot be entirely attributed to their homodynamic effects (19,21). In particular, these maneuvers have been shown to be effective in the attenuation of glomerulosclerosis (...

Licofelone, a novel dual anti‐inflammatory drug that inhibits 5‐lipoxygenase (5‐LOX) and cyclooxygenase (COX), has recently been defined to have therapeutic effects in osteoarthritis. Both 5‐LOX and COX play functional roles in the pathogenesis of glomerulonephritis in children as well. Interleukin‐18 is a pro‐inflammatory cytokine. It remains unclear whether licofelone can ameliorate inflammatory response of human mesangial cells (HMC) exposed to interleukin‐18. In this study, HMC were cultured and exposed to interleukin‐18 with or without pre‐treatment of licofelone. COX‐2 and 5‐LOX enzyme activities in mesangial cells were determined with chromometry or high‐performance liquid chromatography. Prostaglandin E2, cysteinyl leukotriene, monocyte chemotactic protein‐1 and interferon‐γ concentrations in culture medium were measured using an enzyme‐linked immunosorbent assay. Western blotting was employed to detect phosphorylated mitogen‐activated protein kinases ERK1/2, p38 and JNK1/2 in HMC. It was found that licofelone attenuated interleukin‐18‐induced COX‐2 enzyme activity in HMC and prostaglandin E2 release in a dose‐dependent manner. Similarly, licofelone inhibited interleukin‐18‐induced 5‐LOX enzyme activity and leukotriene release. Licofelone reduced interleukin‐18‐induced phosphorylation of p38 mitogen–activated protein kinase and suppressed monocyte chemotactic protein‐1 and interferon‐γ synthesis. Moreover, licofelone inhibited IL‐18‐induced proliferation of mesangial cells. We conclude that licofelone inhibits interleukin‐18‐induced pro‐inflammatory cytokine release and cellular proliferation in HMC, which may represent a really interesting therapeutic approach for glomerulonephritis in children.

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At present, bioinformatics research focuses on the development from the accumulation of biological data to the integration and processing of biological data. This paper designs a bio gene information collection system based on data mining technology. In the system, the information of gene web analysis database, data mining model database and gene chip database is transferred to gene algorithm tool library, which can extract, transform and load the biological gene information, transfer the collected and processed biological gene information to gene general chip and web database analysis logic, and pass it to gene expression spectrum chip/data mining module through API function GUI, through the data mining module GUI feedback to the system users. The system hardware stores the biochip information in the virtual chip set model through the gene expression spectrum data analysis model uses the gene expression similarity analysis model to analyze the expression similarity of the biological gene information, and stores the information in the gene chip database; through the multi-layer structure model, constructs the web genome biochip including the application layer, the data processing layer and the representation layer. The information analysis module analyzes the biological gene information and stores the information in the gene web analysis database. The system software adopts the method of automatic collection of biological gene data based on the web to realize the collection of biological gene information, and gives the main implementation technology of the system. The experimental results show that the system can effectively collect biological gene information, and has high accuracy and anti-noise performance.