|本期目录/Table of Contents|

[1]臧 勇,田 园,李卫东.雷公藤甲素通过调节TGF-β1信号通路和Hippo信号通路影响肾小管上皮细胞的上皮-间充质转化[J].天津医科大学学报,2019,25(03):205-209224.
 ZANG Yong,TIAN Yuan,LI Wei-dong.Triptolide affects epithelial-mesenchymal transition of renal tubular epithelial cells by regulating TGF-β1 and Hippo signaling pathways[J].Journal of Tianjin Medical University,2019,25(03):205-209224.
点击复制

雷公藤甲素通过调节TGF-β1信号通路和Hippo信号通路影响肾小管上皮细胞的上皮-间充质转化(PDF)
分享到:

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
25卷
期数:
2019年03期
页码:
205-209224
栏目:
基础医学
出版日期:
2019-05-20

文章信息/Info

Title:
Triptolide affects epithelial-mesenchymal transition of renal tubular epithelial cells by regulating TGF-β1 and Hippo signaling pathways
文章编号:
1006-8147(2019)03-0205-06
作者:
臧 勇1田 园12 李卫东1
(1.天津医科大学基础医学院遗传学系,天津 300070;2. 贵阳市第一人民医院输血科,贵阳 550002)
Author(s):
ZANG Yong1 TIAN Yuan12 LI Wei-dong1
(1.Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University,Tianjin 300070, China; 2. Department of Blood Transfusion, The First People’s Hospital of Guiyang, Guiyang 550002, China)
关键词:
雷公藤甲素上皮间充质转化纤维化肾小管上皮细胞
Keywords:
triptolideepithelial mesenchymal transformationfibrosisrenal tubular epithelial cells
分类号:
R915
DOI:
-
文献标志码:
A
摘要:
目的:研究雷公藤甲素(TP)对肾小管纤维化抑制作用的机制。方法:将HK-2分成3组,阴性对照组不做处理,TGF-β1组用 TGF-β1处理,TGF-β1+TP组用TGF-β1和TP处理,培养48 h观察细胞的形态,利用RNA 测序技术检测各组中mRNA的表达,通过KEGG基因富集筛选相关通路,用Western blot检测EMT相关蛋白及富集所得信号通路中重要蛋白的表达。结果:TP处理可致HK-2形态改变。RNA测序和KEGG富集分析显示,TP显著影响TGF-β信号通路和Hippo信号通路相关基因的表达。Western blot结果表明TP可影响HK-2细胞EMT相关蛋白、TGF-β1信号通路和Hippo信号通路中的重要指标蛋白的表达。结论:TP可通过调节TGF-β1信号通路和Hippo信号通路抑制肾小管上皮细胞发生上皮-间充质转化。
Abstract:
Objective: To investigate the mechanism of the inhibition of triptolide(TP) on renal tubular fibrosis, by using renal tubular epithelial cells(HK-2) as a model system to identify TP regulated signaling pathways through RNA sequencing and Western blot. Methods: HK-2 cells were divided into 3 groups: the untreated normal control group, the TGF-β1 group(cells were stimulated by 20 ng/mL TGF-β1), and the TGF-β1+TP group(cells were stimulated by 20 ng/mL TGF-β1 and 10 nmol/L TP). Cells were observed by microscope after cultured for 48 h. RNA sequencing was performed to detected mRNA expressions in different groups. KEGG pathway enrichment was performed to analyze the differential expressed genes. Western blot was used to detected the various proteins of EMT, TGF-β1, and Hippo pathway markers. Results: NK-2 cells morphology changed significantly when stimulated by TP. RNA sequencing and KEGG pathway enrichment analyses showed that TP had impacts on TGF-β and Hippo signaling pathways. Expressions of marker proteins of EMT, TGF-β1, and Hippo signaling pathways, such as E-cadherin, N-cadherin, Vimentin, Smad2/3, TGF-βR1, and TAZ were changed significantly when HK-2 cells were stimulated by TP(P<0.05). Conclusion: TP may affect the expressions of TGF-β1 and Hippo signaling pathway hallmark genes, and inhibited the occurrence of EMT that induced by TGF-β1.

参考文献/References:

[1] Yang J, Shultz R W, Mars W M, et al. Disruption of tissue-type plasminogen activator gene in mice reduces renal interstitial fibrosis in obstructive nephropathy[J]. J Clin Invest, 2002, 110(10): 1525
[2] Yang J, Liu Y. Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis[J]. Am J Pathol, 2001, 159(4): 1465
[3] Chen Z H, Qin W S, Zeng C H, et al. Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro[J]. Kidney Int, 2010, 77(11): 974
[4] He J, Xu Y, Koya D, et al. Role of the endothelial-to-mesenchymal transition in renal fibrosis of chronic kidney disease[J]. Clin Exp Nephrol, 2013, 17(4): 488
[5] Hazzan M, Hertig A, Buob D, et al. Epithelial-to-mesenchymal transition predicts cyclosporine nephrotoxicity in renal transplant recipients[J]. J Am Soc Nephrol, 2011, 22(7): 1375
[6] Liu Q. Triptolide and its expanding multiple pharmacological functions[J]. Int Immunopharmacol, 2011, 11(3): 377
[7] 蔡奕, 李帆, 王继周. 前列地尔脂球载体制剂联合洛沙坦、雷公藤多甙对2型糖尿病肾病肾脏血流动力学的干预作用[J]. 今日药学, 2012, 22(8): 478
[8] Leuenroth S J, Okuhara D, Shotwell J D, et al. Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease[J]. Proc Natl Acad Sci U S A, 2007, 104(11): 4389
[9] He L, Peng X, Liu G, et al. Anti-inflammatory effects of triptolide on IgA nephropathy in rats[J]. Immunopharmacol Immunotoxicol, 2015, 37(5): 421
[10] Sun G D, Li C Y, Cui W P, et al. Review of herbal traditional Chinese medicine for the treatment of diabetic nephropathy[J]. J Diabetes Res, 2016, 2016: 5749857
[11] Liu W J, Luo M N, Tan J, et al. Autophagy activation reduces renal tubular injury induced by urinary proteins[J]. Autophagy, 2014, 10(2): 243
[12] Dhawan U, Sue M W, Lan K C, et al. Nanochip-induced epithelial-to-mesenchymal transition: impact of physical microenvironment on cancer metastasis[J]. ACS Appl Mater Interfaces, 2018, 10(14): 11474
[13] Labernadie A, Kato T, Brugues A, et al. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion[J]. Nat Cell Biol, 2017, 19(3): 224
[14] Tang D D, Bai Y, Gunst S J. Silencing of p21-activated kinase attenuates vimentin phosphorylation on Ser-56 and reorientation of the vimentin network during stimulation of smooth muscle cells by 5-hydroxytryptamine[J]. Biochem J, 2005, 388(Pt 3): 773
[15] Indra I, Choi J, Chen C S, et al. Spatial and temporal organization of cadherin in punctate adherens junctions[J]. Proc Natl Acad Sci U S A, 2018, 115(19): E4406
[16] Kanehisa M, Goto S, Sato Y, et al. Data, information, knowledge and principle: back to metabolism in KEGG[J]. Nucleic Acids Res, 2014, 42(Database issue): D199
[17] Genevet A, Tapon N. The Hippo pathway and apico-basal cell polarity[J]. Biochem J, 2011, 436(2): 213
[18] Narimatsu M, Labibi B, Wrana J L, et al. Analysis of Hippo and TGFbeta signaling in polarizing epithelial cells and mouse embryos[J]. Differentiation, 2016, 91(4/5): 109
[19] Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition[J]. Nat Rev Mol Cell Biol, 2014, 15(3): 178
[20] Uemura M, Swenson E S, Gaca M D, et al. Smad2 and Smad3 play different roles in rat hepatic stellate cell function and alpha-smooth muscle actin organization[J]. Mol Biol Cell, 2005, 16(9): 4214
[21] 房勃龙, 韩鸿玲, 张鹏, 等. TGF-β、Smad信号通路蛋白及α-SMA在糖尿病肾病患者肾组织中的表达和意义[J]. 天津医药, 2013, 41(11): 1067
[22] Wieser R, Wrana J L, Massague J. GS domain mutations that constitutively activate T beta R-I, the downstream signaling component in the TGF-beta receptor complex[J]. EMBO J, 1995, 14(10): 2199
[23] Hermann A, Wennmann D O, Gromnitza S, et al. WW and C2 domain-containing proteins regulate hepatic cell differentiation and tumorigenesis through the hippo signaling pathway[J]. Hepatology, 2018, 67(4): 1546
[24] Xu J, Li P X, Wu J, et al. Involvement of the Hippo pathway in regeneration and fibrogenesis after ischaemic acute kidney injury: YAP is the key effector[J]. Clin Sci (Lond), 2016, 130(5): 349
[25] Hirate Y, Hirahara S, Inoue K, et al. Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos[J]. Curr Biol, 2013, 23(13): 1181
[26] Aragona M, Panciera T, Manfrin A, et al. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors[J]. Cell, 2013, 154(5):1047

相似文献/References:

[1]姚晶瑞,姜埃利,王立华,等.雷公藤甲素上调PRDX2抑制2型糖尿病肾病的氧化应激状态[J].天津医科大学学报,2019,25(05):466.
 YAO Jing-rui,JIANG Ai-li,WANG Li-hua,et al.Inhibition of Triptolide on oxidase stress via PRDX2 expression in diabetic nephropathy[J].Journal of Tianjin Medical University,2019,25(03):466.

备注/Memo

备注/Memo:
基金项目 国家重点研发计划项目资助(2017YFC1001900)
作者简介 臧勇(1992-),男,硕士在读,研究方向:病理与病理生理学;通信作者:李卫东,E-mail:liweidong98@tmu.edu.cn;田园,E-mail:1129424744@ qq.com。
更新日期/Last Update: 2019-07-03