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Dynamic Variation of RAS on Silicotic Fibrosis Pathogenesis in Rats

Current Medical Science 2019年第4期39卷 551-559页

作者： Bo-nan ZHANG Xin ZHANG Hong XU Xue-min GAO Gui-zhen ZHANG Hui ZHANG Fang YANG School of Public Health Tangshan Key Laboratory for Clinical and Basic Research on Chronic DiseasesSchool of Basic Medical SciencesNorth China University of Science and TechnologyTangshan 063210China Hebei Key Laboratory for Organ Fibrosis Medical Research CenterTangshan Key Laboratory for Clinical and Basic Research on Chronic DiseasesSchool of Basic Medical SciencesNorth China University of Science and TechnologyTangshan 063210China Hebei Key Laboratory for Chronic Diseases Tangshan Key Laboratory for Clinical and Basic Research on Chronic DiseasesSchool of Basic Medical SciencesNorth China University of Science and TechnologyTangshan 063210China Basic Medical College Hebei Medical UniversityShijiazhuang 050017China

The dynamic variation of renin-angiotensin system (RAS) in silicosis remains *** Wistar rats were divided into 7 groups including control group,silicosis groups (inhaling SiO2 for 2,4,8,16 and 24 weeks,respectively) and Captopril (Cap) *** lung primary fibroblasts were divided into control group,SiO2-stimulated group (0,0.5,1,3,6,12,24 and 48 h) and Cap *** silicotic nodules were formed and collagens were deposited gradually in silicosis group observed by haematoxylin and eosin (HE) staining and Van Gieson (VG) *** relieved the lung fibrosis and collagen *** indicated the positive expression of α-smooth muscle actin α-SMA) was increased gradually in silicotic rat lung *** blotting revealed the expression of collagen type Ⅰ(Col Ⅰ) and α-SMA was up-regulated in silicotic rat lung tissue and fibroblasts stimulated by *** decreased the expression of Col Ⅰ and α-SMA in silicotic rat lung tissue and fibroblasts stimulated by *** blotting also demonstrated the expression of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (ATI) was increased,and the expression of ACE2 and Mas was decreased gradually in silicotic rat lung tissue and fibroblasts stimulated by *** showed the serum levels of ACE and angiotensin Ⅱ(Ang Ⅱ) were also increased and ACE2 and Ang (1 -7) were decreased in the silicosis *** with Cap decreased the expression levels of ACE,Ang Ⅱ and ATI,and increased the expression levels of ACE2,Ang (1-7) and *** findings suggested that an imbalance between ACE-Ang Ⅱ-AT1 axis and ACE2-Ang (l-7)-Mas axis may participate in the development of silicosis.

关键词： silicosis fibroblasts SiCh renin-angiotensin system α-smooth muscle actin

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Daikenchuto (Da-Jian-Zhong-Tang) ameliorates intestinal fibrosis by activating myofibroblast transient receptor potential ankyrin 1 channel

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World Journal of Gastroenterology 2018年第35期24卷 4036-4053页

作者： Keizo Hiraishi Lin-Hai Kurahara Miho Sumiyoshi Yao-Peng Hu Kaori Koga Miki Onitsuka Daibo Kojima Lixia Yue Hidetoshi Takedatsu Yu-Wen Jian Ryuji Inoue Department of Physiology Graduate School of Medical Sciences Fukuoka University Department of Pathology Faculty of Medicine Fukuoka University Department of Gastroenterological Surgery Faculty of Medicine Fukuoka University Department of Cell Biology University of Connecticut Health Center Department of Gastroenterology and Medicine Faculty of Medicine Fukuoka University College of Letters and Science University of CaliforniaDavis

AIM To investigate the anti-fibrotic effects of the traditional oriental herbal medicine Daikenchuto(DKT) associated with transient receptor potential ankyrin 1(TRPA1) channels in intestinal myofibroblasts. METHODS Inflammatory and fibrotic changes were detected in a2,4,6-trinitrobenzenesulfonic acid(TNBS) chronic colitis model of wild-type and TRPA1-knockout(TRPA1-KO) mice via pathological staining and immunoblotting ***^(2+) imaging experiments examined the effects of DKT and its components/ingredients on intestinal myofibroblast(In Myo Fib) cell TRPA1 channel *** factors and transforming growth factor (TGF) -β1-associated signaling were tested in an In Myo Fib cell line by q PCR and immunoblotting *** from non-stenotic and stenotic regions of the intestines of patients with Crohn’s disease (CD) were used for pathological analysis. RESULTS Chronic treatment with TNBS caused more severe inflammation and fibrotic changes in TRPA1-KO than in wild-type mice.A one-week enema administration of DKT reduced fibrotic lesions in wild-type but not in TRPA1-KO *** active ingredients of DKT,i.e.,hydroxyα-sanshool and 6-shogaol,induced Ca^(2+) influxes in In Myo Fib,and this was antagonized by co-treatment with a selective TRPA1 channel blocker,*** counteracted TGF-β1-induced expression of TypeⅠcollagen andα-smooth muscle actin (α-SMA) ,which were accompanied by a reduction in the phosphorylation of Smad-2 and p38-mitogen-activated protein kinase (p38-MAPK) and the expression of ***,24-h incubation with a DKT active component Japanese Pepper increased the m RNA and protein expression levels of TRPA1 in In Myo Fibs,which in turn negatively regulated collagen *** the stenotic regions of the intestines of CD patients,TRPA1 expression was significantly *** The effects of DKT on the expression and activation of the TRPA1 channel could be advantageous for suppressing intestinal fibrosis

关键词： Intestinal fibrosis Myofibroblast Transient receptor potential ankyrin 1 Crohn’s disease Collagen α-smooth muscle actin

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Effect of Quyu Chencuo Formula(去菀陈莝方)on Renal Fibrosis in Obstructive Nephropathy Rats

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Chinese Journal of Integrative Medicine 2019年第3期25卷 190-196页

作者： ZHU Rui DU Xing-guo YANG Sheng-lan WU Yan-ran LIU Jian-guo Department of Traditional Chinese Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology

Objective: To observe the effect of Quyu Chencuo Formula(去菀陈莝方, QCF) on renal fibrosis in rats with obstructive nephropathy. Methods: Twenty-four rats were randomly divided into three groups, 4 for sham operation as the control group, 10 for unilateral ureteral obstruction(UUO) model group, and the rest 10 for QCF treating UUO model group. All rats were sacrificed under 3% pentobarbital(50 mg/kg) anesthesia on the 14 th day after surgery, then the right kidney samples of rats were harvested for hematoxylin eosin(HE) staining and Masson staining to observe the renal pathological changes. Immunohistochemistry and Western blotting were used to examine the expression of transforming growth factor β1(TGF-β1), and real-time polymerase chain reaction(RT-PCR) was employed to examine the expressions of TGF-β1, α-smooth muscle actin(α-SMA) and E-cadherin mRNA. Results: HE and Masson staining showed that the renal interstitial of the rats in the control group had no significant fibrotic lesion; in the model group, there were obvious interstitial fibrosis; for the QCF group, there were epithelial cell necrosis, infiltration of lymphocytes and mononuclear cells, aggravated interstitial fibrosis in varied degrees, but the pathological changes were less in the QCF group than in the model group. The immunohistochemistry and Western blotting results showed that the TGF-β1 expression was increased significantly in the model group, while decreased significantly in the QCF group(P<0.05); RT-PCR showed that the mRNA expression of α-SMA and TGF-β1 increased significantly in the model group, while both were significantly decreased in the QCF group compared with the model group(P<0.05). The mRNA expression of E-cadherin was decreased significantly in the model group, and it was significantly increased in the QCF group as compared with the model group(P<0.05). Conclusion: QCF may improve renal fibrosis by regulating the expressions of TGF-β1, α-SMA and E-cadherin, and prevent the progress o

关键词： unilateral ureteral ligation Quyu Chencuo Formula E-cadherin,transforming growth factor β 1 α-smooth muscle actin kidney fibrosis Chinese medicine

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Epigallocatechin-3-gallate suppresses transforming growth factor-beta signaling by interacting with the transforming growth factor-beta typeⅡreceptor

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World Journal of Experimental Medicine 2013年第4期3卷 100-107页

作者： Masaki Tabuchi Sumio Hayakawa Eiko Honda Kana Ooshima Tatsuki Itoh Koji Yoshida Ah-Mee Park Hideaki Higashino Mamoru Isemura Hiroshi Munakata Department of Biochemistry Kinki University Faculty of Medicine Division of Signaling in Cancer and Immunology Institute for Genetic Medicine Hokkaido University Life Science Research Institute Kinki University Department of Pharmacology Kinki University Faculty of Medicine Department of Pathology Kinki University Faculty of Medicine Graduate School of Nutritional and Environmental Sciences University of Shizuoka

AIM: To investigate the(-)-epigallocatechin-3-gallate(EGCG) binding to transforming growth factor-β(TGF-β) type Ⅱ receptor(TGFRⅡ).METHODS: The expression of α-smooth muscle actin(α-SMA) was used as a marker for fibrotic change inhuman lung fibroblast MRC-5 cells. The α-SMA expression level was determined by western blotting and immunohistological analysis. We examined whether the anti-fibrotic effects of EGCG on MRC-5 cells was dependent on antioxidant mechanism by using edaravone and N-acetylcysteine(NAC). The suppression effects of EGCG on Smad2/3 activation were studied by confocal fluorescence microscopy. The binding of EGCG to recombinant TGFRⅡ protein was analyzed by immunoprecipitation and affinity ***: When MRC-5 cells were treated with TGF-β, EGCG decreased the expression of α-SMA in a dose dependent manner, whereas catechin did not influence the α-SMA expression in the cells. Except for EGCG, antioxidant compounds(e.g., edaravone and NAC) had no effects on the TGF-β-induced α-SMA expression. Nuclear localization of phosphorylated Smad2/3 was observed after TGF-β treatment; however, EGCG treatment attenuated the nuclear transportation of Smad2/3 in the presence or absence of TGF-β. After a TGFRⅡ expression vector was introduced into COS-7 cells, cell lysates were untreated or treated with EGCG or catechin. The immunoprecipitation experiments using the lysates showed that EGCG dose-dependently bound to TGFRⅡ and that catechin did not at all. Affinity chromatography study indicated that EGCG would bind to TGFRⅡ.CONCLUSION: Our results demonstrate that EGCG interacts with TGFRⅡ and inhibits the expression of α-SMA via the TGF-β-Smad2/3 pathway in human lung fibroblast MRC-5 cells.

关键词： Epigallocatechin-3-gallate Transforming growth factor-β Myofibroblast α-smooth muscle actin Fibrosis

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PDGF/ROCK通路介导的肌成纤维细胞分化在大鼠矽肺形成中的作用

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中国医学创新 2015年第16期12卷 13-15页

作者：张丽娟李倩邓海静张文丽王小君裴鑫郝小惠李治国杨方华北理工大学河北唐山063000

目的:探讨PDGF/Rock通路介导的肌成纤维细胞分化在大鼠矽肺纤维化形成中的作用。方法:采用非暴露式气管二氧化硅混悬液灌注法制备大鼠矽肺模型,SPF级健康成年Wistar大鼠40只随机分为四组:模型对照4周组、模型对照8周组、矽肺模型4周组... 详细信息

目的:探讨PDGF/Rock通路介导的肌成纤维细胞分化在大鼠矽肺纤维化形成中的作用。方法:采用非暴露式气管二氧化硅混悬液灌注法制备大鼠矽肺模型,SPF级健康成年Wistar大鼠40只随机分为四组:模型对照4周组、模型对照8周组、矽肺模型4周组、矽肺模型8周组,每组10只。Western blot检测肺组织内α-SMA、phosphoPDGF-β、ROCK、Ⅰ型和Ⅲ型胶原蛋白的表达。结果:大鼠矽肺模型制备成功。与相应对照组相比,矽肺模型组大鼠肺组织内α-SMA、phospho-PDGFR-β、Rock以及Ⅰ型和Ⅲ型胶原蛋白表达均明显增加,比较差异有统计学意义(P<0.05)。结论:PDGF介导的ROCK信号转导通路可能通过促进大鼠肌成纤维细胞转化而促进矽肺大鼠肺组织内的胶原合成,进而促进矽肺纤维化的形成。

关键词：血小板源性生长因子 Rho相关卷曲螺旋形成蛋白激酶 α-平滑肌肌动蛋白肌成纤维细胞矽肺 α-smooth muscle action (α-SMA)

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