全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
-  2018 

钙蛋白酶通过调控蛋白激酶B参与肺纤维化的形成 Calpain Promotes Pulmonary Fibrosis Through Activation of Protein Kinase B

Keywords: 钙蛋白酶,肺间质纤维化,博来霉素,Micro-CT,蛋白激酶B

Full-Text   Cite this paper   Add to My Lib

Abstract:

目的:探讨钙蛋白酶(calpain)在博来霉素诱导的肺纤维化中的作用及其与蛋白激酶B(PKB)的关系。方法:40只雄性C57BL/6小鼠随机分为生理盐水对照组(NS组)、博来霉素处理组(BLM组)、二甲基亚砜对照组(BLM+DMSO组)、钙蛋白酶抑制剂组(BLM+Calpeptin组),各组小鼠予以相应处理后于第28天行Micro-CT以及HE染色检测肺组织纤维化程度,并且通过Western Blot法测定各组小鼠肺组织中calpain-1、calpain-2的表达和PKB的磷酸化水平。结果:(1)与NS组相比,BLM组小鼠肺组织中可见到明显的纤维化改变,纤维化评分高(P<0.01),Calpeptin干预后纤维化程度减轻,纤维化评分降低(P<0.01)。(2)BLM组小鼠肺组织中calpain-1、calpain-2蛋白的表达以及PKB的磷酸化水平均较NS组升高(P<0.01),Calpeptin干预后上述蛋白水平明显下调(P<0.01)。结论:钙蛋白酶通过调控PKB参与博来霉素诱导的肺间质纤维化

References

[1]  Manning BD,Cantley LC.AKT/PKB signaling:navigating downstream[J].Cell,2007,129(7):1 261-1 274.
[2]  Rao SS,Mu Q,Zeng Y,et al.Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodelling in asthma[J].Clin Exp Allergy,2017,47(2):176-189.
[3]  Ashcroft T,Simpson JM,Timbrell V.Simple method of estimating severity of pulmonary fibrosis on a numerical scale[J].J Clin Pathol,1988,41(4):467-470.
[4]  Storr SJ,Carragher NO,Frame MC,et al.The calpain system and cancer[J].Nat Rev Cancer,2011,11(5):364-374.
[5]  Potz BA,Sabe AA,Abid MR,et al.Calpains and coronary vascular disease[J].Circ J,2016,80(1):4-10.
[6]  Li FZ,Cai PC,Song LJ,et al.Crosstalk between calpain activation and TGF-beta1augments collagen-I synthesis in pulmonary fibrosis[J].Biochim Biophys Acta,2015,1 852(9):1 796-1 804.
[7]  Baudry M,Bi X.Calpain-1and Calpain-2:The yin and yang of synaptic plasticity and neurodegeneration[J].Trends Neurosci,2016,39(4):235-245.
[8]  Yang J,Xiang F,Cai PC,et al.Activation of calpain by renin-angiotensin system in pleural mesothelial cells mediates tuberculous pleural fibrosis[J].Am J Physiol Lung Cell Mol Physiol,2016,311(1):L145-L153.
[9]  Hutchinson J,Fogarty A,Hubbard R,et al.Global incidence and mortality of idiopathic pulmonary fibrosis:a systematic review[J].Eur Respir J,2015,46(3):795-806.
[10]  Tabata C,Tabata R,Nakano T.The calpain inhibitor calpeptin prevents bleomycin-induced pulmonary fibrosis in mice[J].Clin Exp Immunol,2010,162(3):560-567.
[11]  Abdalla M,Sabbineni H,Prakash R,et al.The Akt inhibitor,triciribine,ameliorates chronic hypoxia-induced vascular pruning and TGFbeta-induced pulmonary fibrosis[J].Br J Pharmacol,2015,172(16):4 173-4 188.
[12]  Karkkainen M,Kettunen HP,Nurmi H,et al.Effect of smoking and comorbidities on survival in idiopathic pulmonary fibrosis[J].Respir Res,2017,18(1):160.
[13]  Keyvani H,Moghoofei M,Bokharaei-Salim F,et al.Prevalence of respiratory viruses in iranian patients with idiopathic pulmonary fibrosis[J].J Med Microbiol,2017,66(11):1 602-1 606.
[14]  Snider GL,Hayes JA,Korthy AL.Chronic interstitial pulmonary fibrosis produced in hamsters by endotracheal bleomycin:pathology and stereology[J].Am Rev Respir Dis,1978,117(6):1 099-1 108.
[15]  Chua F,Gauldie J,Laurent GJ.Pulmonary fibrosis:searching for model answers[J].Am J Respir Cell Mol Biol,2005,33(1):9-13.
[16]  Averna M,Bavestrello M,Cresta F,et al.Abnormal activation of calpain and protein kinase Calpha promotes a constitutive release of matrix metalloproteinase 9in peripheral blood mononuclear cells from cystic fibrosis patients[J].Arch Biochem Biophys,2016,604:103-112.
[17]  Tsujinaka T,Kajiwara Y,Kambayashi J,et al.Synthesis of a new cell penetrating calpain inhibitor(calpeptin)[J].Biochem Biophys Res Commun,1988,153(3):1 201-1 208.
[18]  Briz V,Hsu YT,Li Y,et al.Calpain-2-mediated PTEN degradation contributes to BDNF-induced stimulation of dendritic protein synthesis[J].J Neurosci,2013,33(10):4 317-4 328.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133