共查询到20条相似文献，搜索用时 31 毫秒
1.
AIM: To investigate the effects of antioxidant N-acetylcysteine (NAC) on the lipopolysaccharide (LPS)-induced MAPK phosphorylation in mouse liver. METHODS: 54 male mice were divided into three groups: control (n=6), 0.9% sodium chloride 0.2 mL ip; LPS group (n=24): LPS 5 mg ip; NAC+LPS group (n=24): NAC 150 mg·kg-1·d-1 ip, for 3 d; LPS 5 mg ip after 1 h of NAC administration at 3rd day. The liver was excised with carbrital anesthesia after LPS or 0.9 % sodium chloride injection at 0.5 h, 1 h, 2 h and 6 h for GSH and MDA assays. The protein extracted from liver was assayed for the phosphorylation of MEK1/2, ERK1/2, p38 MAPK by Western blotting. TNF-α in liver was assayed by radioimmunoassay. RESULTS: MDA in the liver was decreased remarkably and the GSH in the liver was increased significantly by NAC pretreatment. The phosphorylation of MEK1/2, ERK1/2 and p38 MAPK in liver were inhibited significantly by NAC pretreatment after LPS challenge. Meanwhile, TNF-α in liver was decreased markedly. CONCLUSION: Reactive oxygen species plays a critical role in MAPK signaling during the LPS induced acute liver injury. NAC partially inhibits LPS-induced MAPK signaling by antioxidant effect and decreases TNF-α production. 相似文献
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ZHANG Zhao-cai YANG Ying-zhen CHEN Rui-zhen CHENG Lei-lei GE Jun-bo CHEN Hao-zhu 《园艺学报》2006,22(8):1529-1534
AIM：To investigate the dynamic alteration of cardiac collagen metabolism in mice with acute,chronic myocarditis and dilated cardiomyopathy (DCM).METHODS：BALB/c mice infected with coxsackievirus B3 were used to establish animal models of acute,chronic myocarditis and dilated cardiomyopathy,while uninfected animals were also prepared and served as controls.After verification of models by histopathological methods and echocardiography,serum concentration of aminoterminal propeptide of type Ⅲ procollagen (PIIINP),aminoterminal propeptide of type Ⅰ procollagen (PINP) and carboxyterminal propeptide of type I procollagen (PICP) in each group of mice were detected by enzyme linked immunosorbent assay (ELISA).The expression of matrix metalloproteinase 1 (MMP-1) and its tissue inhibitor (TIMP-1) were determined by Western blotting analysis.The MMP-1 activity was also detected.RESULTS：Marked myocardial fibrosis was observed in all groups of CVB3-infected mice.Reparative fibrosis,promotion of synthesis and degradation of cardiac collagens were presented in heart tissue of acute myocarditis mice.Both reparative and reactive fibrosis,enhanced synthesis and lightened degradation of collagen were present in chronic myocarditis,while reactive fibrosis and excess collagen synthesis were confirmed in DCM.Expression and activity of MMP-1 was progressively decreased.TIMP-1 showed unchanged.The ratio of MMP-1/TIMP-1 was progressively descended.CONCLUSION：Collagen metabolism was special in different phase of viral heart diseases,which may play different roles in the progression and prognosis of these kinds of disease. 相似文献
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QI Ben-ling LIU Hong-zhi CAO Lin-sheng CHENG Pei GUAN Si-ming LIU Cheng-yun ZHANG Hu-ping HE Ping WU Jian-ping 《园艺学报》2007,23(4):689-692
AIM: To investigate whether and how AT1 receptor blocker， valsartan， attenuates left ventricular remodeling and failure in a rat model of adriamycin（ADR）-induced dilated cardiomyopathy. METHODS: Weight-matched adult male Wistar rats were randomly divided into 3 groups as follows: 1) the ADR group, in which 2.5 mg/kg of ADR was weekly injected via a tail vein for 10 weeks (n=25); 2) concomitant AT1 receptor blocker valsartan and ADR, in which valsartan was administered by daily gavage at a dose of 30 mg·kg-1·d-1 (n=10); 3) control group (n=10). Hemodynamics and echocardiographic measurements were obtained at 12 weeks after treatment. Finally, left ventricle (LV) samples were collected at 12 weeks. The hydroxyproline content was determined by the methods of chloramines T. The expression of MMP-2, MMP-9 and tissue inhibitors of metalloproteinase-1 (TIMP-1) were measured by Western blotting. MMP-2 and -9 gelatinolytic activities were measured by gelatin zymography. RESULTS: Mortality was significantly lower in valsartan -treated rats than that in ADR rats (20% versus 40%, P<0.01). The dilatation of LV cavity was significantly attenuated in ADR-induced dilated cardiomyopathy rats given valsartan. Valsartan partially normalized LV contractile function, which was significantly reduced in ADR rats. The hydroxyproline content was increased in ADR-DCM group and significantly reduced by valsartan treatment (P<0.01). The protein levels of LV MMP-2 and MMP-9 were increased in ADR rats and attenuated by valsartan treatment (both P<0.01). However, no change in TIMP-1 was observed (P>0.05). The activities of LV myocardial MMP-2 and -9 gelatinolytic were increased significantly in ADR rats (both P<0.01) and attenuated by valsartan treatment (both P<0.01). CONCLUSION: Pretreatment with AT1 receptor blocker valsartan attenuates left ventricular remodeling and failure in a rat model of adriamycin-induced dilated cardiomyopathy. 相似文献
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AIM: To observe the effect of Panax notoginoside (PNS) on the pulmonary artery pressure and the p38 mitogen-activated protein kinase(p38 MAPK) in lung tissues of rats treated with hypoxia. METHODS: Thirty adult male SD rats were randomly divided into 3 groups. The rats in normal control group were exposed to normal conditions, the rats in hypoxia group were exposed to isobaric hypoxia, and the rats in hypoxia+PNS group were treated with PNS under the condition of hypoxia. After 4 weeks of treatment, the mean pulmonary arterial pressure (mPAP) and the mean carotid arterial pressure (mCAP) were measured by cardiac catheterization. The heart was isolated, and the right ventricle (RV), left ventricle plus ventricular septum (LV+S) were weighed to calculate the ratio of RV/(LV+S).The quantity of phospho-p38 MAPK(p-p38 MAPK) in rat pulmonary arterioles was determined by the method of immunohistochemistry and the mRNA content of p38 MAPK was tested by RT-PCR. RESULTS: The mPAP and RV/(LV+S) in hypoxia group were higher than those in normal control group. The expression of p-p38 MAPK in rat pulmonary arterioles and p38 MAPK mRNA in the lung tissues were higher than those in normal control group (P<0.05). The mPAP, RV/(LV+S), the expression of p-p38 MAPK in rat pulmonary arterioles and p38 MAPK mRNA in the lung tissues in hypoxia+PNS group were significantly lower than those in hypoxia group (P<0.05).CONCLUSION: PNS possesses the preventive and therapeutic effect on hypoxic pulmonary hypertension by decreasing p-p38 MAPK and down-regulation of p38 MAPK mRNA in the lungs. 相似文献
5.
SHI Zhe-wei LIU Sheng-xin ZHAN Jia-chen JIN Jia-li CHEN Ying-ying QIN Cheng-fan QIAN Cai-zhen 《园艺学报》2020,36(3):427-432
AIM: To investigate the effect of wogonoside on the inflammatory response of mice with Coxsackie virus B3 (CVB3)-induced myocarditis and its possible regulatory mechanism. METHODS: A mouse model of viral myocarditis was constructed by infecting BALB/c mice with CVB3. BALB/c mice (n =40) were randomized into 4 groups: normal group, CVB3-induced viral myocarditis group, CVB3-induced viral myocarditis combined with wogonoside treatment group and CVB3-induced viral myocarditis combined with wogonoside plus AKT agonist treatment group. All the mice were sacrificed 7 days after treatment. In the first 3 groups, HE staining was applied to detect the infiltration of inflammatory cells in the myocardium, ELISA was applied to detect the serum levels of interleukin-1β (IL-1β) and IL-6, while Western blot was applied to detect the protein expression of inflammatory factors and the activation of AKT/NF-κB pathway. Inaddition, the activation of AKT/NF-κB pathway in the 4 groups was detected by Western blot analysis. RESULTS: HE staining showed that there was a large amount of inflammatory cell infiltration in the myocardium of CVB3-induced viral myocarditis mice, as compared with the normal group, which was significantly reduced by wogonoside treatment (P <0.05). The serum levels of IL-1β and IL-6 in the mice after CVB3 infection were significantly higher than those in normal group (P <0.05), which was also significantly reduced by wogonoside treatment (P <0.05). Western blot analysis indicated that wogonoside treatment significantly reduced the expression of inflammatory factors IL-1β and IL-6, and the phosphorylation of AKT/NF-κB pathway-related proteins in the myocardial tissue (P <0.05). After administration of AKT agonist, the inhibitory effect of wogonoside on NF-κB phosphorylation and inflammatory factors expression was significantly eliminated (P <0.05). CONCLUSION: Wogonoside attenuates the inflammatory response of mice with viral myocarditis by inhibiting the AKT/NF-κB pathway. 相似文献
6.
AIM: To explore the effects of p38 mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinases (PI3K)/Akt on interleukin (IL)-6, the endothelin (ET)-1-mediated process of airway fibroblast activation induced by injured human bronchial epithelial cells (HBE). METHODS: Human primary cultured airway fibroblasts were co-cultured with HBE pre-treated with or without poly-L-arginine (PLA). The procedure was also performed in the presence or absence of p38 MAPK selective inhibitor SB203580, PI3K selective inhibitor LY294002 or ETA receptor blocker BQ123, respectively. Immunostaining, Western blotting or ELISA were used for detecting α-smooth muscle actin (α-SMA) expression, the activities of p38 MAPK and Akt in fibroblasts or IL-6 levels in supernatants of fibroblasts. In addition, fibroblasts were mixed with soluble collagen and cultured with HBE treated as the same mentioned above, the gel contraction was measured by serial area measurements. RESULTS: ET-1 and IL-6 levels ［(13.69±1.36) ng/L, (56.7±10.7) ng/L］ in the supernatants of fibroblasts cultured with injured HBE were significantly higher than those in the supernatants of fibroblasts cultured with HBE ［(3.79±0.64) ng/L, (15.5±3.2) ng/L］. BQ123, SB203580 or LY294002 decreased IL-6 levels ［(27.2±3.1) ng/L, (31.5±3.6) ng/L, (41.3±3.2) ng/L］ differently in the supernatants of fibroblasts induced by injured HBE. Activation of p38 MAPK preceded Akt in fibroblasts cultured with injured HBE. BQ123 reduced the phosphorylation levels of p38 MAPK and Akt. SB203580 concentration-dependently attenuated Akt phosphorylation, while LY294002 had little effect on p38 MAPK phosphorylation. Fibroblasts expressed more α-SMA after cultured with injured HBE and showed significant increase in the gel contraction compared to fibroblasts cultured with HBE ［percentage of gel contraction: (61.2±2.7)% vs (15.4±7.3)%］, all these effects were diminished or inhibited by BQ123, SB203580 or LY294002. Furthermore, the effects of BQ123 and SB203580 on decreased gel contraction were stronger than the effect of LY294002. CONCLUSION: ET-1 exerts a key role in the airway fibroblasts activation induced by injured HBE through activating p38 MAPK, PI3K/Akt signaling and promoting IL-6 expression. 相似文献
7.
黄瓜CsSUN和CsLNG1调控果实大小的机理分析 总被引：2，自引：0，他引：2
对黄瓜Q30（CsSUN/CsLNG1）及以其为遗传背景的3个近等基因系材料，即Q30（CsSUN/CsLNG1）、QK1.2-S（Cssun/CsLNG1）、QK2.1-S（CsSUN/Cslng1）、QK1.2+2.1-S（Cssun/Cslng1）进行组织形态、内源激素和转录水平的分析结果表明：与QK1.2-S和QK2.1-S相比，Q30果实最为细长，茎粗最小，植株最高。在果实各发育期，Q30的细胞最小，而细胞密度最大。Q30在开花前6 d的BR/ABA及GA3/ABA显著低于3个近等基因系，随着果实发育差异逐渐缩小。各材料ZT/ABA和IAA/ABA在果实发育各时期基本无显著差异。开花前6 d和开花当天Q30的CsSUN表达量均显著高于QK1.2-S和QK1.2+2.1-S，CsLNG1表达量显著高于QK1.2-S，整体来看也高于QK1.2+2.1-S；与细胞膨胀相关的基因Csa1G422480（木葡聚糖内转葡糖基酶基因）、Csa6G014540（扩张蛋白基因）、BR生物合成基因Csa1G524640和GA3调节基因Csa3G872170的定量分析结果却相反，在子房期Q30中的表达量显著低于3个近等基因系。随着果实发育，Q30的CsSUN表达水平与QK1.2-S和QK1.2+2.1-S差异逐渐缩小，CsLNG1与QK2.1-S和QK1.2+2.1-S差异也逐渐缩小，而Csa1G422480、Csa6G014540、Csa1G524640、Csa3G872170表达水平反而逐渐上升，后期甚至显著高于3个近等基因系。综上所述，CsSUN和CsLNG1控制Q30黄瓜细长果实是由于子房期抑制了细胞增大，导致细胞体积小，细胞密度增大；进入果实迅速增长期后该基因对细胞大小的抑制作用减弱，在原有数量基础上细胞逐渐变大，果实持续增长。 相似文献
8.
ZHAO Pei SONG Guo-jie GONG Kai-zheng LV Xiao-lei DONG Zhi-feng LIU Jian SUN Hong-guang YU Xiao-ping DING Yong-ling BU Ping ZHANG Zhen-gang 《园艺学报》2008,24(4):697-700
AIM: To explore the effects of pentoxifylline (PTX) on ventricular remodeling and cardiac function in dilated cardiomyopathy (DCM) rats.METHODS: Lewis rats were randomly allocated to a myocin-induced dilated cardiomyopathy (DCM) group receiving saline (n=10), a DCM group receiving PTX (PTX group; 25 mg·kg-1·d-1, ip, for 30 days, n=10) or healthy control group (n=10). The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 in the blood plasma were analyzed by ELISA. The extent of fibrosis was estimated using Massons staining and immunohistochemistry analyses. Cardiac structure and function were measured by echocardiography.RESULTS: PTX decreased plasma levels of TNF-α and IL-6, and increased IL-10 level in DCM animals compared with DCM group ［TNF-α: (7.21±0.24) μg/L vs (19.30±1.31) μg/L, P<0.01; IL-6: (119.60±36.58) ng/L vs (189.50±13.25) ng/L, P<0.05; IL-10: (41.26±3.27) μg/L vs (32.45±4.32) μg/L, P<0.05］. Collagen volume fraction (CVF), perivascular collagen area (PVCA) and collagen Ⅰ/Ⅲ ratio were lower in PTX group than those in DCM group ［CVF: (16.45±3.01)% vs (23.33±4.43)%, P<0.05; PVCA: 4.58±2.10 vs 13.74±4.29, P<0.05; Ⅰ/Ⅲ ratio: 2.84±0.67 vs 4.22±0.54, P<0.01］. Left ventricular end-diastolic dimension reduced ［(6.11±0.51) mm vs (6.46±0.28) mm, P<0.05］ and left ventricular ejection fraction elevated ［(77.29±5.20)% vs (62.73±10.11)%, P<0.01］ by PTX compared with DCM.CONCLUSION: PTX modulates plasma levels of inflammatory cytokines, delays the ventricle remodeling and improves the heart function in DCM rats. 相似文献
9.
AIM: To investigate the effect of epigallocatechin-3-gallate (EGCG) on lipopolysaccharide (LPS)-induced p38 MAPK activation and tumor necrosis factor-α (TNF-α) secretion in macrophages. METHODS: Western blotting was used to detect the phosphorylation of p38 MAPK in mouse macrophages cultured in vitro. Enzyme linked immunosorbent assay was used to determine the secretion of TNF-α in macrophages. Electron microscopy was used to study the effect of EGCG on the structure of LPS. RESULTS: LPS caused activation of p38 MAPK and more production of TNF-α, EGCG inhibited LPS-induced phosphorylation of p38 MAPK and TNF-α production and had no effect on the structure of LPS. CONCLUSIONS: EGCG has no direct effect on LPS, but blocks cellular signal pathway. The inhibition of EGCG on LPS-induced TNF-α production is mediated, at least in part, through blocking of p38 MAPK pathway. 相似文献
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DU Hui-bo SONG Wen ZHANG Li-min XING Li-qiang ZHANG Hui ZHAO Zi-gang NIU Chun-yu 《园艺学报》2014,30(4):686-692
AIM: To observe the effects of normal mesenteric lymph (NML) on the lung, heart and liver injuries and the phosphorylation levels of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) in the mice with endotoxic shock (ES). METHODS: The NML was drained form health male BALB/c mice for the intervention of ES after the removal of cellular constituent. Lipopolysaccharide (LPS, 35 mg/kg) was intraperitoneally injected into the mice for the establishment of ES model. After 60 min of LPS injection, the administration of NML (1/15 of whole blood volume) was performed through the femoral artery in NML+ES group. Meanwhile, the mean arterial pressure (MAP) was monitored during the experiment. At 6 h after intraperitoneal injection of LPS or the corresponding time point, blood samples were harvested from the heart through apical centesis for determination of the biochemical indexes to reflect myocardial and hepatocyte injuries. Simultaneously, the lung, heart and liver tissue specimens from a fixed location were harvested for the observation of histomorphology and the measurement of phosphorylation levels of p38 MAPK, ERK1/2 and JNK. RESULTS: Compared with sham shock (SS) group, MAP in ES group and NML+ES group remarkably decreased at multiple time points after intraperitoneal injection of LPS. However, MAP in NML+ES group at 80 min, 90 min, 190 min, 210 min, 240 min, 250 min, 340 min, 350 min, and 360 min were significantly increased compared with ES group. There were normal structures in the lung, liver and myocardium of the mice in SS group, while the morphological damages of these tissues appeared in ES group. Meanwhile, the damages were attenuated in the mice of NML+ES group. The activities of AST, ALT and CK-MB in the plasma in ES group were remarkably higher than those in SS group. The CK-MB activity in NML+ES group was also increased compared with SS group, and the activities of AST and LDH-1 were lower than those in ES group. At 6 h after LPS injection, the phosphorylation levels of p38 MAPK, ERK1/2 and JNK in the lung tissues were remarkably increased. Meanwhile, no statistical difference of these indexes between the myocardial and hepatic tissues was observed. NML intervention decreased the phosphorylation levels of p38 MAPK in the lung tissues, and p38 MAPK, ERK1/2 and JNK in the myocardial tissues. CONCLUSION: The NML administration alleviates multi-organ injuries and reduces the phosphorylation level of p38 MAPK in the lung tissues in the mice subjected to ES. 相似文献
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AIM: To examine the role of glucocorticoid receptor (GR) in regulation of lipopolysaccharide (LPS)-induced lung injury. METHODS:Male Sprague-Dawley rats were divided into six groups randomly: control group (n=6), LPS group (n=6 each), Dex+LPS group (n=6 each), RU486 group (n=6), RU486+LPS group (n=6 each) and RU486+Dex+LPS group (n=6 each). All groups were subjected into 1 h, 3 h, 6 h and 12 h time point subgroups after LPS administration, except of control group and RU486 group. The concentrations of TNF-α and IL-6 in bronchoalveolar lavage fluids (BALF) were detected by ELISA. The histopathologic changes of lung tissues, the activation of p38MAPK and the expression of MKP-1 in lung tissue were also observed. Further, to confirm the role of GR in this model, the mortality of rats in LPS group vs RU486+LPS group and in Dex+LPS group vs RU486+Des+LPS group was compared. RESULTS: LPS induced lung injury and the secretions of TNF-α and IL-6 in BALF, which were significantly enhanced by pretreatment of RU486 (P<0.05). RU486 pretreatment also significantly increased the LPS-induced lethality (P<0.05). Dexamethasone attenuated LPS-induced lung damage, cytokine release and mortality rates, and the protective effects might be mediated by GR. Western blotting analysis showed dexamethasone inhibited the phosphorylation of p38MAPK in lung tissues by induction of MKP-1, and these actions were also GR dependent. CONCLUSION: GR plays an essential role in regulation of LPS-induced acute lung injury. Anti-inflammatory effects of hormone-activated GR may be mediated by inhibition of p38MAPK phosphorylation/activation, which is associated with the induction of MKP-1. 相似文献
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AIM: To observe the effects of carvedilol on murine viral myocarditis model. METHODS: A total of 188 inbred male BALB/c mice of 4-6 weeks were divided into 4 groups: myocarditis group (group C, n=60), metoprolol treatment group (group M, n=60), carvedilol treatment group (group K, n=60), control group (group B, n=8). Myocardial histopathololgic changes were observed. The concentrations of cardiac troponin I (cTn-I) were detected by chemiluminescence immunoassay (CLIA). Western blotting was performed to analyze the contents of phosphorylated p38MAPK in myocardium. RESULTS: Metropolol and carvedilol lightened myocardial histopathololgic changes at acute stage, decreased cTn-I concentrations and myocardial phosphorylated p38MAPK value compared with myocarditis group. Treatment with carvedilol was more effective than treated with metropolol on those indexes. CONCLUSION: Carvedilol protects against viral myocarditis by inhibition of p38MAPK signal transduction pathway through blockade of β1 and β2 adrenergic receptors. 相似文献
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AIM:To investigate the role of p38 MAPK in cisplatin-induced rat renal proximal tubular cell (RPTC) apoptosis. METHODS:To determine the optimal concentration of cisplatin to induce RPTC apoptosis, the cells were treated with 0, 5, 10 and 20 μmol/L cisplatin for 24 h, and then the cell lysates were collected for Western blot analysis of cleaved PARP, p38 and phosphor ylated p38 (p-p38). To determine the role of p38 MAPK in cisplatin-induced RPTC apoptosis, the cells were divided into control group, cisplatin group (the cells were treated with cisplatin for 24 h) and cisplatin+p38 MAPK inhibitor group (the cells were treated with p38 MAPK inhibitor SB203580 for 1 h, and then treated with cisplatin for another 24 h). The morphological changes of apoptotic cells were observed under phase-contrast fluorescence microscope. The apoptotic rate of the cells were analyzed by flow cytometry. The caspase activity of RPTC lysates was examined using Ac-DEVD-AFC kit. The protein levels of p-p38, p38, cleaved PARP and cleaved caspase-3 were determined by Western blot. The pH value of extracellular environment of the cells was measured by pH meter. RESULTS:Cisplatin at 20 μmol/L obviously induced apoptosis of RPTC. The p38 MAPK was phosphorylated and its phosphorylation peaked at 15 min after cisplatin treatment. The apoptotic rate of RPTC was 12.08% after cisplatin induction. Cisplatin treatment also enhanced caspase activity, and increased cleavage of PARP and caspase-3 proteins (P<0.05). The p38 MAPK inhibitor SB203580 effectively inhibited the phosphorylation of p38 MAPK, down-regulated the RPTC apoptosis rate and caspase activity, and reduced the cleavage of PARP and caspase-3 proteins. The pH value change in RPTC culture medium was also inverted by SB203580. CONCLUSION:The phosphorylation of p38 MAPK is involved in cisplatin-induced apoptosis of RPTC. The apoptosis induced by cisplatin results in the change of acidic extracellular environment, which is inhibited by p38 MAPK inhibitor SB203580. 相似文献
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AIM: The present study was designed to determine whether Sini decoction (SND), a traditional Chinese medicine, induces delayed preconditioning-like effect in rat heart and the possible mechanism by which ischemia myocardium is protected. METHODS: Sprage－Dawleyt rats underwent three 5 min episodes of preconditioning ischemia 24 h prior to the global ischemia and reperfusion in ischemic preconditioning/second window of protection (IPC/SWOP) group or were pretreated with Sini decoction (5 mL·kg-1·d-1 for 3 days, the last treatment 24 h before global ischemia and reperfusion) in SND group. Myocardial infarct size, CK, LDH and NO were examined. p38 MAPK and PKC were determined by immunohistochemisty. RESULTS: Myocardial infarct size was significantly decreased, CK and LDH were decreased in the serum, NO2-/NO3- was increased in myocardial tissue in SND group as well as in IPC/SWOP group (there was no difference between the two groups). The expression of p38 MAPK and PKC were upregulated in myocardial tissue in SND and IPC/SWOP groups. CONCLUSION: These results suggest that Sini decoction induces delayed preconditioning-like effect in the rat heart, possibly via inducing p38 MAPK activation. 相似文献
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AIM: To explore the role of endothelin-1 (ET-1) in initiating transdifferentiation of sub-epithelial fibroblasts (SEFs) into myofibroblasts and its ionic and signal transduction mechanism.METHODS: Human SEFs or SEFs plated in collagen gels were co-cultured with human bronchial epithelial cells (16HBE) treated with lipopolysaccharide (LPS) plus mechanical scratch. ET receptor A inhibitor (BQ123) or the inhibitors specific for p38 MAPK, ERK1/2 were added, repectively. The expression of α-smooth muscle actin (α-SMA) in the SEFs and contractility of the collagen gels containing with SEFs as well as the effects of p38 MAPK or ERK1/2 on α-SMA expression were evaluated. Using Ca2+ sensitive Fluo-3/AM, dynamic changes of intracellular calcium concentration (［Ca2+］i) were observed in the SEFs by laser confocal microscopy.RESULTS: Injured 16HBE induced the transdifferentiation of myofibroblasts, which expressd α-SMA and increased contractility. BQ123 blocked the induction to a certain extent. Injured 16HBE activated p38 MAPK and ERK1/2 pathways in SEFs, both inhibitors of p38 MAPK and ERK1/2 attenuated the induction of α-SMA by injured 16HBE. The addition of exogenous ET-1 enhanced α-SMA expression and activated p38 MAPK, ERK1/2 pathways in the SEFs. Additionally, ET-1 significantly facilitated Ca2+ inflow into the fibroblasts.CONCLUSION: Injured 16HBE induces the transdifferentiation of SEFs into myofibroblasts, which is involved in the activation of p38 MAPK and ERK1/2 pathways. The ET-induced influx of Ca2+ may be an early signal for initiating the myofibroblasts transdifferentiation. 相似文献
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DING Wen-fei SONG Lei LIU Hai-yun QIN Jian-hua CAO Ling GAO Li-chao OU San-tao WU Wei-hua 《园艺学报》2019,35(7):1248-1253
AIM:To investigate the effect of transforming growth factor-β (TGF-β) activated kinase 1(TAK1) on renal tubular epithelial fibrosis. METHODS:The renal tubular epithelial cell line HK-2 was used as the research object. After induced by TGF-β1, real-time PCR and Western blot were used to detect the expression of TAK1 in the HK-2 cells. TAK1 shRNA lentivirus was used to infect HK-2 cells, real-time PCR and Western blot were used to determine the interference effect on TAK1 expression in the HK-2 cells with TGF-β1 stimulation. Under the condition of treating with p38 MAPK activator anisomycin, the levels of type I collagen and type Ⅲ collagen in the supernatant, and the protein levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF) and p-p38MAPKThr 180/Tyr 182 in the HK-2 cells with TAK1 knock-down were determined by ELISA and Western blot, respectively. RESULTS:TGF-β1 significantly increased the expression of TAK1 in the HK-2 cells(P<0.05). TAK1 shRNA significantly decreased the expression of TAK1 in the HK-2 cells with TGF-β1 stimulation. Type I collagen and type Ⅲ collagen secreted by the HK-2 cells after treatment with TGF-β1 were increased, the protein levels of α-SMA, CTGF and p-p38MAPKThr 180/Tyr 182 were also increased(P<0.05). Knock-down of TAK1 expression significantly inhibited the secretion of type I and type Ⅲ collagen, reduced the protein levels of α-SMA, CTGF and p-p38MAPKThr 180/Tyr 182 in the TGF-β1-induced HK-2 cells(P<0.05). Treatment with p38 MAPK activator reversed the inhibitory effect of TAK1 knock-down on the secretion of type I and type Ⅲ collagens, and the protein levels of α-SMA, CTGF and p-p38 MAPKThr 180/Tyr 182 in the HK-2 cells(P<0.05). CONCLUSION:Knock-down of TAK1 expression attenuates the TGF-β1 induced fibrosis of renal tubular epithelial cells by inhibiting p38 MAPK signaling pathway. 相似文献
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AIM: To investigate the anticancer effect of manumycin on abdominal metastatic breast cancer cell line - SK-BR-3 and its relationship with p38 MAPK. METHODS: The test of anticancer effect was performed by the method of MTT, apoptosis induced by manumycin and affected by SB203580, a specific p38 MAPK inhibitor, were examined by caspase-3 activity assay kit, and the protein expression was detected by immunoblotting assay. RESULTS: The inhibition rates at 24 h after treatment with manumycin of 6 μmol/L, 18 μmol/L, 54 μmol/L were (7.4±3.9)%, (21.0±4.4)% and (64.7±4.1)%, respectively and showed dosage-effect relationship. Compared with the control group, the survival rates of the last two treatment groups were decreased significantly (P<0.01). The value of IC50 24 h after treatment with manumycin was 42.5 μmol/L. Manumycin simultaneously activated caspase-3 protein, which was partly blocked by p38 MAPK inhibitor, SB203580. The results of immunoblotting showed that manumycin increased p38 MAPK protein phosphorylation. CONCLUSION: Manumycin exerts anticancer effect on SK-BR-3 cell line via inducing cell apoptosis, which is partly regulated by p38 MAPK. 相似文献
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AIM: Using the mouse model of lipopolysaccharide(LPS) attack,we study the effect of Kupffer cell (KC) blockade on the activation of mitogen-activated protein kinases(MAPKs) signal transduction pathway induced by LPS.METHODS: GdCl3 (10 mg/kg) or the same volume of NS was continually injected intravenously at 48 h and 24 h before LPS (5 mg/kg) was injected into the male mice of Kunming species.The liver was then took out and KCs were isolated 30 minute after LPS was injected.The KCs isolated from the mice were cultured,and pretreated with GdCl3 (100 μmol/L) for 1 h.The culture medium containing LPS (100 μg/L) was added and continuously incubated for 30 minute.The protein expression and phosphorylation level of ERK1/2 and p38MAPK in liver or KCs were assayed in vivo and in vitro,and effect of GdCl3 on the phagocytosis function was observed,respectively.RESULTS: LPS induced the protein phosphorylation of ERK1/2 and p38MAPK in KCs or liver,no effect on the protein expression was observed.GdCl3 treatment inhibited LPS-induced KCs activation and secretion of TNF-α,however,it had no effect on ERK1/2 and p38MAPK in KCs or liver,neither at the protein expression nor the phosphorylation.KCs secreted a few TNF-α with short time treatment with GdCl3 alone in vitro.CONCLUSION: KC blockade with GdCl3 alleviates LPS-induced KCs activation and the release of TNF-α not through modulating intracellular ERK1/2 or p38MAPK signal transduction pathways.We presume that GdCl3 might reduce liver injury through cross talk of other intracellular signal transduction pathways (JNK,NF-кB,GPCR,etc). 相似文献