[1]刁俊玲,伍 敏,黄荣凤,等.新型PPARγ激动剂CMHX008对高糖诱导人肾小管上皮HK-2细胞纤维化的影响及机制[J].中国药理学通报,2019,(10):1363-1369.[doi:10.3969/j.issn.1001-1978.2019.10.008]
 DIAO Jun-ling,WU Min,HUANG Rong-feng,et al.Effect of a novel PPARγ partial agonist CMHX008 on hyperglycemia-induced fibrogenesis in renal tubular epithelial HK-2 cells and its mechanism[J].Chinese Pharmacological Bulletin,2019,(10):1363-1369.[doi:10.3969/j.issn.1001-1978.2019.10.008]
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新型PPARγ激动剂CMHX008对高糖诱导人肾小管上皮HK-2细胞纤维化的影响及机制()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年10期
页码:
1363-1369
栏目:
论著
出版日期:
2019-09-15

文章信息/Info

Title:
Effect of a novel PPARγ partial agonist CMHX008 on hyperglycemia-induced fibrogenesis in renal tubular epithelial HK-2 cells and its mechanism
文章编号:
1001-1978(2019)10-1363-07
作者:
刁俊玲1伍 敏1黄荣凤1廖茂霖1陈春秀12李佳渝1李继斌2肖晓秋1
重庆医科大学1.附属第一医院重大代谢性疾病转化医学重庆市高校重点实验室、2.公共卫生与管理学院,重庆 400016
Author(s):
DIAO Jun-ling1 WU Min1 HUANG Rong-feng1 LIAO Mao-lin1 CHEN Chun-xiu12 LI Jia-yu1 LI Ji-bin2 XIAO Xiao-qiu1
1.Chongqing Key Lab of Translational Medicine in Major Metabolic Disease, the First Affiliated Hospital of Chongqing Medical University; 2.School of Public Health and Management, Chongqing Medical University, Chongqing 400016, China
关键词:
糖尿病肾病 高糖 罗格列酮 PPARγ 肾小管上皮细胞 纤维化
Keywords:
diabetic nephropathy high glucose rosiglitazone PPARγ renal tubular epithelial cells fibrosis
分类号:
R322.61; R329.24; R587.1; R692.39; R977.15; R977.6
DOI:
10.3969/j.issn.1001-1978.2019.10.008
文献标志码:
A
摘要:
目的 本研究以罗格列酮为对照,探讨新型PPARγ激动剂CMHX008对高糖诱导人肾小管上皮HK-2细胞纤维化标志的影响及机制。方法 罗格列酮和CMHX008处理高糖培养的HK-2细胞,CCK-8法检测不同药物浓度处理后的细胞存活率; 免疫印迹法检测纤维化标志蛋白和磷酸化PPARγ(Ser273)的表达; qRT-PCR检测纤维化指标mRNA的表达; 划痕和Transwell侵袭实验检测HK-2细胞迁移和侵袭能力的变化。结果 CCK-8法结果显示,3 μmol·L-1罗格列酮和3 μmol·L-1 CMHX008对HK-2细胞均无明显细胞毒性; 免疫印迹法显示,给予罗格列酮和CMHX008能逆转高糖条件下PPARγ(Ser273)磷酸化的上调,减少TGF-β1、α-SMA的表达,增加E-cadherin的表达; 划痕和Transwell实验显示,罗格列酮和CMHX008可以抑制高糖引起HK-2细胞迁移和侵袭能力的增强。结论 与罗格列酮类似,新型PPARγ激动剂CMHX008能抑制高糖引起的HK-2细胞纤维化标志物的上调,减弱细胞的迁移和侵袭能力,提示CMHX008有改善糖尿病引起肾脏纤维化的作用,其机制可能与抑制PPARγ(Ser273)磷酸化有关。
Abstract:
Aim To investigate the effect of CMHX008, a novel peroxisome proliferator-activated receptor γ(PPARγ)partial agonist, on fibrogenic pathways and its potential mechanism in renal tubular epithelial HK-2 cells in comparison with rosiglitazone.Methods HK-2 cells were cultured with 30 mmol·L-1 D-(+)-glucose, and then treated with rosiglitazone and CMHX008.Cell counting kit-8(CCK-8)was used to detect cell viability; immunoblotting was used to detect protein expression fibrogenic markers and p-PPARγ(ser273)in HK-2 cells; quantitative real time PCR(qRT-PCR)was used to detect fibrosis-related mRNA levels; wound healing assay and transwell assay were used to detect the migration and invasion ability of HK-2 cells.Results CCK-8 analysis showed that 3 μmol·L-1 rosiglitazone and 3 μmol·L-1 CMHX008 had no obvious cytotoxicity to HK-2 cells; immunoblotting revealed that rosiglitazone and CMHX008 could reverse the up-regulation of p-PPARγ(ser273), reduce transforming growth factor β1(TGF-β1)and α-smooth muscle actin(α-SMA)protein levels, and up-regulate E-cadherin protein expression levels in HK-2 cells in high glucose conditions; wound healing assay and transwell assay showed that rosiglitazone and CMHX008 could inhibit the increase of migration and invasion ability of hyperglycemia-cultured HK-2 cells.Conclusions The novel PPARγ agonist CMHX008 can improve hyperglycemia-induced renal tubular fibrosis, which may be possibly related to the inhibition of p-PPARγ(Ser273)phosphorylation.

参考文献/References:

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备注/Memo

备注/Memo:
收稿日期:2019-04-14,修回日期:2019-07-15 基金项目:国家自然科学基金面上项目(No 81570763); 重庆市基础与前沿研究计划项目(No cstc2015 jcy jBX0132) 作者简介:刁俊玲(1993-),女,硕士生,研究方向:代谢性疾病的发病机制和干预对策,E-mail:928935038@qq.com; 肖晓秋(1964-),男,博士,教授,博士生导师,研究方向:代谢性疾病的发病机制和干预对策,通讯作者,E-mail: bshaw2001@163.com
更新日期/Last Update: 2019-09-15