ABSTRACT
<p><b>OBJECTIVE</b>To examine the transfection of Homeobox A13 (HOXA13) on epithelial-mesenchymal transition (EMT) and the expression of bone morphogenetic protein-7 (BMP-7) induced by albumin-overload in human kidney tubular epithelial cells (HKCs).</p><p><b>METHODS</b>The cultured HKCs were treated with 20 mg/mL human serum albumin (HSA) for 48 hours. Protein expression of cytokeratin (CK), vimentin and HOXA13 in the HKCs was assessed by Western blot. Protein expression of CK, vimentin, and BMP-7 was also detected in HKCs transfected with lipofectamine contained HOXA13 DNA.</p><p><b>RESULTS</b>HSA induced EMT in HKCs, presented by decreased CK expression (P<0.01) and increased vimentin expression (P<0.01). The up-regulated expression of HOXA13 transfected by lipofectamine inhibited the level of EMT induced by HSA in HKCs (P<0.05). The decreased rate of BMP-7 protein expression induced by HSA was inhibited by over-expressed HOXA13 in HKCs (P<0.05).</p><p><b>CONCLUSIONS</b>Transfection of HOXA13 in HKCs could inhibit the degree of EMT induced by albumin-overload, possibly by increasing BMP-7 expression.</p>
Subject(s)
Humans , Bone Morphogenetic Protein 7 , Genetics , Cells, Cultured , Epithelial Cells , Metabolism , Epithelial-Mesenchymal Transition , Homeodomain Proteins , Physiology , Keratins , Genetics , Kidney Tubules , Metabolism , Transfection , Vimentin , GeneticsABSTRACT
In the previous study, a high-throughput screening method was established to find the antagonists of CD36. In the present study, a new compound named IMB-1680 was found using this method. The anti-atherosclerotic activities of IMB-1680 were then evaluated. Dose-dependent activities of IMB-1680 were detected by using Sf9 [hCD36] and CHO [hCD36] models. Fluorescence microscopic photography and flow cytometry were used to analyze uptake of mLDL. Foam cell test with RAW264.7 macrophages was used to examine lipid accumulation. The results showed that IMB-1680 inhibited CD36 activity with IC50 of 2.80 and 8.79 micromol x L(-1) in Sf9[hCD36] and CHO [hCD36] cells, respectively. Fluorescence microscopic photography and flow cytometry revealed that IMB-1680 could significantly reduce DiI-AcLDL uptake. Meanwhile, IMB-1680 also could reduce lipids accumulation in RAW264.7 macrophages. In all, the data indicated that IMB-1680 might be a potent effective anti-atherosclerotic leading compound.
Subject(s)
Animals , Humans , Mice , CD36 Antigens , Genetics , Metabolism , CHO Cells , Cells, Cultured , Cricetulus , Dose-Response Relationship, Drug , Foam Cells , Cell Biology , High-Throughput Screening Assays , Lipoproteins, LDL , Metabolism , Macrophages , Cell Biology , Metabolism , Molecular Structure , Plasmids , Receptors, Scavenger , Sf9 Cells , Spodoptera , TransfectionABSTRACT
Objective: To search for new compounds with better water-solubility and higher antianxiety activities. Methods: A series of 2-arylimidazo[1,2-a] pyridine-3-acetamide derivitives were designed and synthesized. The anxiolytic activities were evaluated by BZDR competitive binding assay in vitro and the elevated-plus maze test in mice, the structure-activity relationship (SAR) has been studied. Results and Conclusion: Twenty-eight new compounds have been synthesized. Their structures were confirmed by 1H NMR and MS. According to the results of BZDR affinity test, compounds I1, I 8, I10, I13, I19 showed as good affinity as the positive control (Ro5-4864). The corresponding inhibition was 87%, 89%, 85%, 89% and 76% respectively at the concentration of 100 nmol/L, while that of Ro5-4864 was 82%. I8 and I10, which display better water-solubility and better BZDR affinity in vitro, show significant antianxiety effects in vivo.