• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂可减弱转化生长因子β1（TGF-β1）在肾间质成纤维细胞中诱导的促纤维化反应。

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists attenuate the profibrotic response induced by TGF-beta1 in renal interstitial fibroblasts.

作者信息

Wang Weiming, Liu Feng, Chen Nan

机构信息

Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

Mediators Inflamm. 2007;2007:62641. doi: 10.1155/2007/62641.

DOI:10.1155/2007/62641
PMID:18274641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2220083/
Abstract

BACKGROUND

Studies have shown that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists could ameliorate renal fibrotic lesions in both diabetic nephropathy and nondiabetic chronic kidney diseases. In order to elucidate the antifibrotic mechanism of PPAR-gamma agonists, we investigated the effects of PPAR-gamma activation on TGF-beta1-induced renal interstitial fibroblasts.

METHODS

In rat renal interstitial fibroblasts (NRK/49F), the mRNA expression of TGF-beta1-induced alpha-smooth muscle actin (alpha-SMA), connective tissue growth factor (CTGF), fibronectin (FN) and collagen type III (Col III) were observed by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein expressions of FN and Smads were observed by Western blot.

RESULTS

In NRK/49F, TGF-beta1 enhanced CTGF, FN and Col III mRNA expression in a dose- and time-dependent manner. alpha-SMA, CTGF, FN and Col III mRNA and FN protein expression in 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2)-troglitazone- and ciglitazone-pretreated groups, respectively, were significantly decreased compared with the TGF-beta1-stimulated group. TGF-beta1 (5 ng/mL) enhanced p-Smad2/3 protein expression in a time-dependent manner. Compared with the TGF-beta1-stimulated group, p-Smad2/3 protein induced by TGF-beta1 in PPAR-gamma agonists-pretreated groups significantly decreased with no statistical difference amongst the three pretreated groups.

CONCLUSION

PPAR-gamma agonists could inhibit TGF-beta1-induced renal fibroblast activation, CTGF expression and ECM synthesis through abrogating the TGF-beta1/Smads signaling pathway.

摘要

背景

研究表明，过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂可改善糖尿病肾病和非糖尿病慢性肾脏病中的肾纤维化病变。为阐明PPAR-γ激动剂的抗纤维化机制，我们研究了PPAR-γ激活对转化生长因子β1（TGF-β1）诱导的肾间质成纤维细胞的影响。

方法

在大鼠肾间质成纤维细胞（NRK/49F）中，通过逆转录聚合酶链反应（RT-PCR）观察TGF-β1诱导的α-平滑肌肌动蛋白（α-SMA）、结缔组织生长因子（CTGF）、纤连蛋白（FN）和Ⅲ型胶原（ColⅢ）的mRNA表达。通过蛋白质印迹法观察FN和Smads的蛋白表达。

结果

在NRK/49F中，TGF-β1以剂量和时间依赖性方式增强CTGF、FN和ColⅢ的mRNA表达。与TGF-β1刺激组相比，15-脱氧-Δ12,14-前列腺素J2（15d-PGJ2）、曲格列酮和吡格列酮预处理组的α-SMA、CTGF、FN和ColⅢ的mRNA以及FN蛋白表达均显著降低。TGF-β1（5 ng/mL）以时间依赖性方式增强p-Smad2/3蛋白表达。与TGF-β1刺激组相比，PPAR-γ激动剂预处理组中TGF-β1诱导的p-Smad2/3蛋白显著降低，三个预处理组之间无统计学差异。

结论

PPAR-γ激动剂可通过废除TGF-β1/Smads信号通路来抑制TGF-β1诱导的肾成纤维细胞活化、CTGF表达和细胞外基质合成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/6eccb90edd80/MI2007-62641.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/64689032ed68/MI2007-62641.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/222d5ca32bd8/MI2007-62641.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/07a1ed73fddd/MI2007-62641.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/d9117864f1be/MI2007-62641.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/916c6561c05b/MI2007-62641.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/721df90dd5ca/MI2007-62641.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/6eccb90edd80/MI2007-62641.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/64689032ed68/MI2007-62641.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/222d5ca32bd8/MI2007-62641.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/07a1ed73fddd/MI2007-62641.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/d9117864f1be/MI2007-62641.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/916c6561c05b/MI2007-62641.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/721df90dd5ca/MI2007-62641.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4259/2220083/6eccb90edd80/MI2007-62641.007.jpg

相似文献

1
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists attenuate the profibrotic response induced by TGF-beta1 in renal interstitial fibroblasts.过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂可减弱转化生长因子β1（TGF-β1）在肾间质成纤维细胞中诱导的促纤维化反应。
Mediators Inflamm. 2007;2007:62641. doi: 10.1155/2007/62641.
2
[Effects of peroxisome proliferators-activated receptor gamma agonists on transforming growth factor-beta1 and Smads signal pathway: experiment with rat renal fibroblasts].过氧化物酶体增殖物激活受体γ激动剂对转化生长因子-β1及Smads信号通路的影响：大鼠肾成纤维细胞实验
Zhonghua Yi Xue Za Zhi. 2006 Mar 21;86(11):740-4.
3
hepatocyte growth factor is a downstream effector that mediates the antifibrotic action of peroxisome proliferator-activated receptor-gamma agonists.肝细胞生长因子是一种下游效应分子，介导过氧化物酶体增殖物激活受体γ激动剂的抗纤维化作用。
J Am Soc Nephrol. 2006 Jan;17(1):54-65. doi: 10.1681/ASN.2005030257. Epub 2005 Nov 16.
4
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist inhibits transforming growth factor-beta1 and matrix production in human dermal fibroblasts.过氧化物酶体增殖物激活受体-γ（PPAR-γ）激动剂可抑制人真皮成纤维细胞中转化生长因子-β1 和基质的产生。
J Plast Reconstr Aesthet Surg. 2010 Jul;63(7):1209-16. doi: 10.1016/j.bjps.2009.06.032. Epub 2009 Jul 18.
5
[Mechanism underlying the inhibitory effects of peroxisome proliferator-activated receptor γ agonists on transforming growth factor β1 in adult skin fibroblasts].[过氧化物酶体增殖物激活受体γ激动剂对成年皮肤成纤维细胞中转化生长因子β1抑制作用的潜在机制]
Zhonghua Shao Shang Za Zhi. 2010 Dec;26(6):448-51.
6
Troglitazone inhibits synthesis of transforming growth factor-beta1 and reduces matrix production in human peritoneal mesothelial cells.曲格列酮可抑制转化生长因子-β1的合成，并减少人腹膜间皮细胞中的基质产生。
Nephrology (Carlton). 2006 Dec;11(6):516-23. doi: 10.1111/j.1440-1797.2006.00654.x.
7
A PPAR-Gamma Agonist Rosiglitazone Suppresses Fibrotic Response in Human Pterygium Fibroblasts by Modulating the p38 MAPK Pathway.一种过氧化物酶体增殖物激活受体γ激动剂罗格列酮通过调节p38丝裂原活化蛋白激酶途径抑制人翼状胬肉成纤维细胞的纤维化反应。
Invest Ophthalmol Vis Sci. 2017 Oct 1;58(12):5217-5226. doi: 10.1167/iovs.17-22203.
8
Anti-fibrogenic effect of PPAR-γ agonists in human intestinal myofibroblasts.过氧化物酶体增殖物激活受体γ激动剂对人肠肌成纤维细胞的抗纤维化作用
BMC Gastroenterol. 2017 Jun 7;17(1):73. doi: 10.1186/s12876-017-0627-4.
9
Antifibrotic Actions of Peroxisome Proliferator-Activated Receptor γ Ligands in Corneal Fibroblasts Are Mediated by β-Catenin-Regulated Pathways.过氧化物酶体增殖物激活受体γ配体在角膜成纤维细胞中的抗纤维化作用由β-连环蛋白调节的途径介导。
Am J Pathol. 2017 Aug;187(8):1660-1669. doi: 10.1016/j.ajpath.2017.04.002. Epub 2017 Jun 10.
10
Curcumin ameliorates renal fibrosis by inhibiting local fibroblast proliferation and extracellular matrix deposition.姜黄素通过抑制局部成纤维细胞增殖和细胞外基质沉积来改善肾纤维化。
J Pharmacol Sci. 2014;126(4):344-50. doi: 10.1254/jphs.14173FP. Epub 2014 Dec 2.

引用本文的文献

1
Deciphering per- and polyfluoroalkyl substances mode of action: comparative gene expression analysis in human liver spheroids.解读全氟和多氟烷基物质的作用模式：人肝球状体中的比较基因表达分析
Toxicol Sci. 2025 May 1;205(1):124-142. doi: 10.1093/toxsci/kfaf023.
2
Advancing therapeutic frontiers: a pipeline of novel drugs for luminal and perianal Crohn's disease management.推进治疗前沿：用于治疗回肠和肛周克罗恩病的新型药物研发进程
Therap Adv Gastroenterol. 2024 Dec 19;17:17562848241303651. doi: 10.1177/17562848241303651. eCollection 2024.
3
Antrodia cinnamomea extract alleviates bleomycin-induced pulmonary fibrosis in mice by inhibiting the mTOR pathway.

本文引用的文献

1
Apoptosis and proliferation of cultured mesangial cells isolated from kidneys of rosiglitazone-treated pregnant diabetic rats.罗格列酮治疗的妊娠糖尿病大鼠肾脏中分离出的培养系膜细胞的凋亡与增殖
Nephrol Dial Transplant. 2006 May;21(5):1198-204. doi: 10.1093/ndt/gfk084. Epub 2006 Jan 31.
2
Pioglitazone lowers systemic asymmetric dimethylarginine by inducing dimethylarginine dimethylaminohydrolase in rats.吡格列酮通过诱导大鼠体内二甲基精氨酸二甲胺水解酶降低全身不对称二甲基精氨酸水平。
Hypertens Res. 2005 Mar;28(3):255-62. doi: 10.1291/hypres.28.255.
3
Pioglitazone attenuates TGF-beta(1)-induction of fibronectin synthesis and its splicing variant in human mesangial cells via activation of peroxisome proliferator-activated receptor (PPAR)gamma.
樟芝提取物通过抑制mTOR通路减轻博来霉素诱导的小鼠肺纤维化。
Biomed J. 2024 Dec;47(6):100720. doi: 10.1016/j.bj.2024.100720. Epub 2024 Apr 26.
4
Pioglitazone Protects Tubular Epithelial Cells during Kidney Fibrosis by Attenuating miRNA Dysregulation and Autophagy Dysfunction Induced by TGF-β.吡格列酮通过减轻 TGF-β诱导的 miRNA 失调和自噬功能障碍来保护肾小管上皮细胞免受肾纤维化的影响。
Int J Mol Sci. 2023 Oct 24;24(21):15520. doi: 10.3390/ijms242115520.
5
PPAR Pan Agonist MHY2013 Alleviates Renal Fibrosis in a Mouse Model by Reducing Fibroblast Activation and Epithelial Inflammation.PPAR 全激动剂 MHY2013 通过减少成纤维细胞激活和上皮炎症缓解小鼠模型的肾纤维化。
Int J Mol Sci. 2023 Mar 2;24(5):4882. doi: 10.3390/ijms24054882.
6
The efficacy of pioglitazone for renal protection in diabetic kidney disease.吡格列酮在糖尿病肾病中的肾脏保护作用。
PLoS One. 2022 Feb 17;17(2):e0264129. doi: 10.1371/journal.pone.0264129. eCollection 2022.
7
Shentong Zhuyu Decoction Inhibits Inflammatory Response, Migration, and Invasion and Promotes Apoptosis of Rheumatoid Arthritis Fibroblast-like Synoviocytes via the MAPK p38/PPAR/CTGF Pathway.伸筋逐瘀汤通过 MAPK p38/PPAR/CTGF 通路抑制类风湿关节炎成纤维样滑膜细胞炎症反应、迁移和侵袭并促进其凋亡。
Biomed Res Int. 2021 Jan 15;2021:6187695. doi: 10.1155/2021/6187695. eCollection 2021.
8
PPAR and Its Agonists in Chronic Kidney Disease.过氧化物酶体增殖物激活受体及其激动剂在慢性肾脏病中的作用
Int J Nephrol. 2020 Feb 25;2020:2917474. doi: 10.1155/2020/2917474. eCollection 2020.
9
15-Deoxy-∆--Prostaglandin J2 (15d-PGJ2), an Endogenous Ligand of PPAR-: Function and Mechanism.15-脱氧-Δ¹²-前列腺素J2（15d-PGJ2），过氧化物酶体增殖物激活受体-γ的内源性配体：功能与机制
PPAR Res. 2019 Aug 1;2019:7242030. doi: 10.1155/2019/7242030. eCollection 2019.
10
The PPARγ agonist pioglitazone prevents TGF-β induced renal fibrosis by repressing EGR-1 and STAT3.过氧化物酶体增殖物激活受体γ激动剂吡格列酮通过抑制 EGR-1 和 STAT3 预防 TGF-β诱导的肾纤维化。
BMC Nephrol. 2019 Jul 5;20(1):245. doi: 10.1186/s12882-019-1431-x.
吡格列酮通过激活过氧化物酶体增殖物激活受体（PPAR）γ，减弱转化生长因子-β1（TGF-β1）诱导的人肾小球系膜细胞中纤连蛋白合成及其剪接变体。
Cell Biol Int. 2005 Jun;29(6):422-8. doi: 10.1016/j.cellbi.2005.01.005. Epub 2005 Mar 31.
4
Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4-activated transcription and profibrogenic effects of connective tissue growth factor.己酮可可碱通过阻断Smad3/4激活的转录和结缔组织生长因子的促纤维化作用来减轻肾小管间质纤维化。
J Am Soc Nephrol. 2005 Sep;16(9):2702-13. doi: 10.1681/ASN.2005040435. Epub 2005 Jun 29.
5
PPARgamma agonists exert antifibrotic effects in renal tubular cells exposed to high glucose.过氧化物酶体增殖物激活受体γ（PPARγ）激动剂对暴露于高糖环境的肾小管细胞具有抗纤维化作用。
Am J Physiol Renal Physiol. 2005 Nov;289(5):F1153-8. doi: 10.1152/ajprenal.00097.2005. Epub 2005 May 10.
6
Transforming growth factor-beta and Smad signalling in kidney diseases.转化生长因子-β 与 Smad 信号通路在肾脏疾病中的作用
Nephrology (Carlton). 2005 Feb;10(1):48-56. doi: 10.1111/j.1440-1797.2005.00334.x.
7
Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts.吡格列酮抑制人肾成纤维细胞的细胞生长并减少基质产生。
J Am Soc Nephrol. 2005 Mar;16(3):638-45. doi: 10.1681/ASN.2004040278. Epub 2005 Feb 2.
8
Peroxisome proliferator-activated receptors ligands, oxidative stress, and cardiac fibroblast extracellular matrix turnover.过氧化物酶体增殖物激活受体配体、氧化应激与心脏成纤维细胞细胞外基质周转
Hypertension. 2004 Nov;44(5):621-2. doi: 10.1161/01.HYP.0000144401.18602.67. Epub 2004 Sep 20.
9
Smad3 as a mediator of the fibrotic response.Smad3作为纤维化反应的介质。
Int J Exp Pathol. 2004 Apr;85(2):47-64. doi: 10.1111/j.0959-9673.2004.00377.x.
10
TGF-beta signaling and the fibrotic response.转化生长因子-β信号传导与纤维化反应。
FASEB J. 2004 May;18(7):816-27. doi: 10.1096/fj.03-1273rev.