Inhibitory Effects for Rheumatoid Arthritis of Dietary Supplementation with Resveratrol in Collagen-induced Arthritis

OBJECTIVE: Resveratrol is well-known for its anti-inflammatory, anti-oxidant effects on several diseases. We investigated whether dietary supplementation with resveratrol may suppress joint inflammation and destruction in a mouse model of collagen-induced arthritis (CIA). METHODS: Mice were randomly divided into two groups; CIA mice with normal diet-fed and CIA mice fed a 0.05% resveratrol diet. The effect of resveratrol on arthritis was assessed by clinical scoring system. The plain radiographs of paws were obtained to evaluate the effects on preventing bone destruction. Joint inflammation, cartilage damage, and osteoclastic bone resorption were checked by staining with H&E, Safranin-O, and tartrate resistant acid phosphatase (TRAP). Levels of pro-inflammatory cytokines were checked by enzyme-linked immunosorbent assay. The level of expression of nuclear factor (NF)-kappaB was measured by electrophoretic mobility shift assay (EMSA). RESULTS: Dietary supplementation with resveratrol led to mitigated severity of arthritis compared to the normal diet group (6.7+/-0.8 vs. 2.7+/-0.6, p<0.01). Resveratrol-fed mice showed decreased bone destruction on radiograph (3.4+/-0.3 vs. 2.0+/-0.2, p<0.01), and showed significantly inhibited pathological changes (inflammation 2.0+/-0.3 vs.3.2+/-0.2, p<0.01; cartilage damage 1.5+/-0.3 vs. 3.2+/-0.2, p<0.01; pannus formation 1.4+/-0.3 vs. 3.0+/-0.3, p<0.01; erosion; 1.4+/-0.2 vs. 3.3+/-0.3, p<0.01). Generation of TRAP-positive osteoclasts was inhibited in the resveratrol-fed mice (55.3+/-12.7 vs. 3.27+/-0.8, p<0.01). Resveratrol-fed mice showed decreased levels of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6,monocyte chemoattractant protein 1, and the soluble receptor activator of NF-kappaB ligand in joint tissues and sera. Expression of NF-kappaB, measured by EMSA, was decreased in resveratrol-fed mice. CONCLUSION: Dietary supplementation with resveratrol mitigates inflammation and bone destruction in CIA mice.

Expression of Platelet Derived Growth Factor-A, C and Platelet Derived Growth Factor Receptor-alpha in the Ischemia Reperfusion Renal Failure Model / 대한신장학회잡지

BACKGOUND: Platelet-derived growth factor (PDGF) is a widely expressed growth factor with both mitogenic and chemotactic activities in many connective tissue cell types. There are four members of PDGF family; PDGF-A, PDGF-B, PDGF-C, PDGF-D. Their biological effects are mediated via two tyrosine kinase receptors, PDGF receptor-alpha and PDGF receptor-beta, and PDGF-mediated signaling is critical for development of many organ systems and acquired disease. The aims of this study were to determine the changes of PDGF-A, PDGF-C and PDGF receptor (PDGFR)-alpha expression in ischemia reperfusion acute renal failure model. METHODS: We examined the expression and localization of PDGF-A, PDGF-C and PDGF receptor-alpha protein using Western blot analysis and immunohistochemistry and PDGF-C mRNA using RNase protection assay after ischemia reperfusion renal failure model. RESULTS: PDGF-A expression showed no change after ischemia reperfusion injury. Proliferating cell nuclear antigen expression increased at day 2 after ischemia reperfusion injury. PDGF-C expression increased at day 2 after ischemia reperfusion injury, and was localized in tubular epithelial cells of outer medulla. PDGFR-alpha increased at day 2 after ischemia reperfusion injury, and was localized in tubular interstitium of outer medulla. CONCLUSION: These results indicated that PDGF-C and PDGF receptor-alpha may have an important role in the renal regeneration after ischemia reperfusion renal injury.

The Expressions of PDGF-C, PDGF-D and PDGF Receptors in Renal Development Model / 대한신장학회잡지

BACKGROUND: Four platelet derived growth factor (PDGF) family members have been identified; the classical PDGFs, PDGF-A and PDGF-B, and the novel PDGFs, PDGF-C and PDGF-D, which were only recently discovered. METHODS: The present study was designed to determine the changes of the platelet derived growth factor (PDGF) subtypes (C & D) and their receptors (PDGFR)-alpha & beta expression in kidneys during pre- and postnatal development. RESULTS: All the protein levels of PDGFR-alpha and -beta and the mRNA levels of PDGF-C and D were high in kidneys during the prenatal period and decreased differently during the postnatal period. PDGFR-alpha was expressed in the interstitial space at embryo day 18. PDGFR-beta protein were expressed in metanephric blastema at embryo day 18. PDGF-C mRNA was expressed in metanephric blastema, developing glomerulus at embryo 18 day and in collecting duct at postnatal day 7. PDGF-D mRNA was expressed in the parietal and vesceral epithelial cells during pre and postnatal period. CONCLUSION: These results indicate that the PDGF subtypes (C & D) and their receptors (PDGFR-alpha & -beta) are differently expressed in the kidney during the prenatal and postnatal period.

The Study on the Expression of Angiopoietin-1, Angiopoietin-2, and Tie2 in Mouse Kidney Maturation / 대한신장학회잡지

BACKGROUND: The Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2) and Tie2 have essential role in angiogenesis in development. Ang1 and Ang2 are ligands which binds to their receptor, Tie2. METHODS: Expression of these proteins was sought during mouse kidney maturation from embryonic day 16 (E16) to 28 days postnatal (P28). RESULTS: Using RNase protection assay and Western blot, these three molecules were expressed throughout the experimental period with peak levels at P28 (Ang1), P14 (Ang2) and P7 (Tie2). By immunohistochemical analysis, Ang1 protein was found to localize to condensing renal mesenchymal cells, and tubules. Ang2 proteins were detected in differentiating outer medullary tubules and the vasa recta bundle area. Tie2 protein was detected in a portion of glomerular tufts and cortical interstitium, and medulla including vessels in the vasa recta. CONCLUSIONS: These data suggest that Ang1, Ang2 and Tie2 proteins are expressed in renal development.