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AIM:To investigate the expression of FIZZ1 ( found in inflammatory zone 1) in the lung tissues from smoking-induced chronic obstructive pulmonary disease (COPD) rats and to explore the potential role of FIZZ1 in air-way remodeling in COPD. METHODS:The male Wistar rats (n=70) were used in the study. The rats were randomly di-vided into COPD group and control group. The rat model of COPD was established by inhaling cigarette smoke alone. HE staining was used to observe the pathological changes of the lung tissues for firming the successful modeling. The protein ex-pression of FIZZ1 in the lung tissues at different time points was determined by immunohistochemistry and Western blot. The inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted. The concentrations of interleukin 4 (IL-4) and tumor necrosis factor α (TNF-α) in both BALF and serum were measured by ELISA. RESULTS:HE staining showed that the inflammatory response was chronic in the lung tissues of model group at 20th week and gradually showed pathologi-cal features of COPD. The results of immunohistochemistry and Western blot showed that in the model group, FIZZ1 protein expression was significantly increased (P<0. 05). Total number of inflammatory cells in BALF in the cigarette smoked rats was significantly higher from 4th week (P<0. 05). Within a certain range, compared with the control group, the concen-trations of inflammatory cytokines IL-4 and TNF-α in both BALF and serum were increased in the model group ( P <0.05). CONCLUSIONS:FIZZ1 may be involved in the occurrence and development of COPD with the mechanism of causing infiltration of inflammatory cells and secretion of cytokines.
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AIM:To investigate the RELMα/FIZZ1 signaling pathway on the regulation of the Ca 2+/CaM sig-naling pathway in the mouse aortic smooth muscle cells MOVAS and on the formation of blood vessels in the mouse aortic endothelial cells(MAEC).METHODS:The MAEC cultured in vitro were divided into pGSadeno-HK group,pGSadeno-RELMα/FIZZ1 group,pGSadeno-shRNA control group and pGSadeno-shRNA RELMα/FIZZ1 group.MTT assay was used to detect the viability of the MAEC.The formation of stroma tubes was observed for determining angiogenesis.The MOVAS cells cultured in vitro were also divided into pGSadeno-HK group,pGSadeno-RELMα/FIZZ1 group,pGSadeno-shRNA con-trol group and pGSadeno-shRNA RELMα/FIZZ1 group.The viability of MOVAS cells was measured by MTT assay.Fluo-3 AM fluorescence probe was used to detect intracellular Ca 2+concentration.The expression of calmodulin(CaM)and my-osin light chain kinase(MLCK)at mRNA and protein levels was determined by real-time PCR and Western blot.RE-SULTS:Over-expression of RELMα/FIZZ1 significantly promoted the viability of the MAEC.The number of lumen forma-tion was increased significantly(P<0.05).Knockdown of the RELM α/FIZZ1 expression inhibited the viability and lumen formation of MAEC(P <0.05).Over-expression of RELMα/FIZZ1 significantly promoted the viability of the MOVAS cells,enhanced the mean fluorescence intensity of intracellular Ca 2+,and the expression of CaM and MLCK at mRNA and protein levels was significantly increased.Knockdown of the RELMα/FIZZ1 expression significantly inhibited the viability of the MOVAS cells,the mean fluorescence intensity of Ca 2+was decreased, the expression of CaM and MLCK at mRNA and protein levels was decreased significantly(P<0.05).CONCLUSION:RELMα/FIZZ1 signaling pathway is involved in the angiogenesis,and the mechanism may be related to the changes of intracellular Ca 2+concentration and then to regu-late the intracellular CaM and MLCK expression.
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Objective To investigate the effects of Schistosoma japonicum infection on selective activation of macrophages and insulin resistance in liver tissues of mice with high-fat diet induced obesity and the possible mechanism. Methods Thirty-six male C57BL/ 6J mice were randomly divided into 3 groups in-cluding normal control group(NC group,n=12),high-fat diet feeding group(HF group,n=12)and high-fat diet feeding with Schistosoma japonicum infection group(HSj group,n=12). Specimens were collected 6 and 12 weeks after high-fat diet feeding. The levels of fasting blood glucose(FBG),fasting plasma insulin (FINS)and homeostasis model assessment for insulin resistance index(HOMA-IR)were detected. The ex-pression of interleukin-6(IL-6),arginase-1(Arg-1)and found in inflammatory zone-1(Fizz-1)at mRNA and protein levels were detected by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR)and immunohistochemistry,respectively. Results The mice from HF group showed higher levels of HOMA-IR than those form NC group and HSj group by the end of 6 and 12 weeks after infection(P﹤0. 05). The levels of HOMA-IR in mice from HF group were increased by the end of week 12 after infection as com-pared with those at week 6(P>0. 05). The levels of IL-6 in mice from both HF group and HSj group were higher than those from NC group by the end of week 6 after infection(P﹤0. 05). Higher levels of IL-6 were detected in mice from HF group as compared with those from HSj group and NC group by the end of week 12 after infection(P﹤0. 05). The expression of Arg-1 and Fizz-1 in mice form HF group were lower than those from NC group by the end of 6 and 12 weeks after infection(P﹤0. 05). Arg-1 was highly expressed in mice form HSj group,followed by those from NC and HF groups 12 weeks after infection. The expression of Fizz-1 in mice from HSj group was the highest among the three groups by the end of week 6 and 12 after infection (P﹤0. 05). Conclusion The proinflammatory effects on mice with diet induced obesity were induced dur-ing acute infection of Schistosoma japonicum cercariae(6 weeks). The chronic infection of Schistosoma ja-ponicum cercariae(12 weeks)might be helpful in reversing hepatic insulin resistance in mice with diet in-duced obesity by changing the polarity of macrophages in liver tissues.
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Background FIZZ1 is a newly found protein associated with pulmonary inflammation. It has been shown to involve in proliferation of pulmonary arterial vascular smooth cells, contriction of vascular vessels, and stimulation of fibroblasts. Objective This study was designed to investigate the expression of FIZZ1 in atherosclerotic plaque of C57BL/6J ApoE-/-mice and the role of FIZZ1 on the proliferation of vascular smooth muscle cells obtained from aorta. Methods Nine C57BL/6J ApoE-/-mice were fed with high fat diet and nine C57BL/6J wild type mice with normal chow for 24 weeks. All mice were euthanized and the aortas were collected. HE stain histological examination and FIZZ1 immunohistochemistry were used in vivo study. In vitro, smooth muscle cells were treated with normal saline (control groups) or recombinate FIZZ1 at different concentrations (final concentration 3?10-6, 9?10-6, 2.7?10-5 mmol/L) respectively. The proliferation of smooth muscle cells were detected by MTT. Results After 24 weeks of high fat diet treatment, large atherosclerotic plaques were found in aortic root of ApoE-/-mice. FIZZ1 was found in atherosclerotic plaques of C57BL/6J ApoE-/-mice, however, no FIZZ1 was expressed in the arteries of C57BL/6J wild type mice. Cell culture study showed FIZZ1 promoted the proliferation of smooth muscle cells in a dose dependent manner(P
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Background Found in Inflammatory Zone 1(FIZZ1)is a newly found protein associated with pulmonary inflammation.We previously had reported its role in the development of atherosclerosis,but its detailed mechanism has not been explored.Objective This study was designed to delineate the effect of FIZZ1 on the expression of scavenger receptor(SR-A)in vascular smooth muscle cells(VSMC)scavenger receptor(SR-A)induced by ox-LDL.Methods Smooth muscle cells were treated with ox-LDL(20 mg/L)or cocultured with recombinate FIZZ1 at different concentration(final concentration 3?10-6,9?10-6,2.7?10-5 mmol/L).The expression of SR-A of smooth muscle cell was detected by flow cytometry and laser confocal microscopy.Results SR-A positive expression was found in VSMCs treated with ox-LDL after 24 hours,which were located mainly in cell membrane by laser confocal microscopy.FIZZ1 significantly accentuate the LDL induced increases in SR-A positive rate in VSMC in a dose dependent manner(P
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AIM: To investigate the expression of FIZZ1/RELM? in lung tissue of chronic cigarette smoking rat,and to determine the relationship between airway inflammation and airway hyperresponsiveness.METHODS: Made rat model of chronic cigarette smoking was used.The expression of FIZZ1/RELM? in lung tissue was determined by immuno-histochemistry and in situ hybridization.RESULTS: In control rats,FIZZ1/RELM? protein and mRNA expressions were observed at low levels.In cigarette smoking rats,FIZZ1/RELM? expression increased in all the cells especially in bronchial smooth muscle cells,vascular wall cells and alveolar epithelial cells.CONCLUSION: FIZZ1/RELM? is a secreted peptide specifically expressed in lung.Cigarette smoking induces its upregulation,which possibly contributes to cigarette smoking-induced airway hyperresponsiveness.