• 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

格列本脲诱导高糖刺激的系膜细胞中IV型胶原的分解代谢。

Glibenclamide induces collagen IV catabolism in high glucose-stimulated mesangial cells.

作者信息

Zhu Liping, Cortes Pedro, Hassett Clare, Taube David W, Yee Jerry

机构信息

Division of Nephrology and Hypertension, Department of Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.

出版信息

Exp Diabetes Res. 2012;2012:183535. doi: 10.1155/2012/183535. Epub 2012 Sep 12.

DOI:10.1155/2012/183535
PMID:23008698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3447387/
Abstract

We have shown the full prevention of mesangial expansion in insulin-deficient diabetic rats by treatment with clinically-relevant dosages of glibenclamide (Glib). Studies in mesangial cells (MCs) also demonstrated reduction in the high glucose (HG)-induced accumulation of collagens, proposing that this was due to increased catabolism. In the present study, we investigated the signaling pathways that may be implicated in Glib action. Rat primary MCs were exposed to HG for 8 weeks with or without Glib in therapeutic (0.01 μM) or supratherapeutic (1.0 μM) concentrations. We found that HG increased collagen IV protein accumulation and PAI-1 mRNA and protein expression, in association with decreased cAMP generating capacity and decreased PKA activity. Low Glib increased collagen IV mRNA but fully prevented collagen IV protein accumulation and PAI-1 overexpression while enhancing cAMP formation and PKA activity. MMP2 mRNA, protein expression and gelatinolytic activity were also enhanced. High Glib was, overall, ineffective. In conclusion, low dosage/concentration Glib prevents HG-induced collagen accumulation in MC by enhancing collagen catabolism in a cAMP-PKA-mediated PAI-1 inhibition.

摘要

我们已经证明，通过给予临床相关剂量的格列本脲（Glib），可完全预防胰岛素缺乏型糖尿病大鼠的系膜扩张。对系膜细胞（MCs）的研究也表明，高糖（HG）诱导的胶原蛋白积累减少，推测这是由于分解代谢增加所致。在本研究中，我们调查了可能与Glib作用相关的信号通路。将大鼠原代MCs暴露于HG环境8周，同时分别添加治疗浓度（0.01μM）或超治疗浓度（1.0μM）的Glib。我们发现，HG会增加IV型胶原蛋白的蛋白积累以及PAI-1的mRNA和蛋白表达，同时伴有cAMP生成能力降低和PKA活性下降。低剂量Glib会增加IV型胶原蛋白的mRNA，但能完全阻止IV型胶原蛋白的蛋白积累和PAI-1的过表达，同时增强cAMP的形成和PKA活性。MMP2的mRNA、蛋白表达及明胶酶活性也得到增强。总体而言，高剂量Glib无效。总之，低剂量/低浓度的Glib通过增强cAMP-PKA介导的PAI-1抑制作用来促进胶原蛋白分解代谢，从而预防HG诱导的MCs中胶原蛋白的积累。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/5ad519a63ecb/EDR2012-183535.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/902c0f36dc92/EDR2012-183535.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/45e1beeaad4c/EDR2012-183535.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/0aae313cf88f/EDR2012-183535.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/38b46a57213e/EDR2012-183535.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/5ad519a63ecb/EDR2012-183535.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/902c0f36dc92/EDR2012-183535.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/45e1beeaad4c/EDR2012-183535.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/0aae313cf88f/EDR2012-183535.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/38b46a57213e/EDR2012-183535.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb7/3447387/5ad519a63ecb/EDR2012-183535.005.jpg

相似文献

1
Glibenclamide induces collagen IV catabolism in high glucose-stimulated mesangial cells.格列本脲诱导高糖刺激的系膜细胞中IV型胶原的分解代谢。
Exp Diabetes Res. 2012;2012:183535. doi: 10.1155/2012/183535. Epub 2012 Sep 12.
2
Glibenclamide prevents increased extracellular matrix formation induced by high glucose concentration in mesangial cells.格列本脲可防止高糖浓度诱导的系膜细胞细胞外基质形成增加。
Am J Physiol Renal Physiol. 2007 Jan;292(1):F57-65. doi: 10.1152/ajprenal.00210.2006. Epub 2006 Aug 8.
3
Rosiglitazone prevents advanced glycation end products-induced renal toxicity likely through suppression of plasminogen activator inhibitor-1.罗格列酮可能通过抑制纤溶酶原激活物抑制剂-1来预防晚期糖基化终产物诱导的肾毒性。
Toxicol Sci. 2007 Apr;96(2):346-56. doi: 10.1093/toxsci/kfm010. Epub 2007 Jan 29.
4
High glucose stimulates cell proliferation and Collagen IV production in rat mesangial cells through inhibiting AMPK-K signaling.高糖通过抑制AMPK-K信号通路刺激大鼠系膜细胞的增殖和IV型胶原蛋白的产生。
Int Urol Nephrol. 2017 Nov;49(11):2079-2086. doi: 10.1007/s11255-017-1654-3. Epub 2017 Jul 26.
5
Effects of long-term elevated glucose on collagen formation by mesangial cells.
Kidney Int. 2007 Nov;72(10):1216-25. doi: 10.1038/sj.ki.5002517. Epub 2007 Aug 29.
6
Rosiglitazone prevents high glucose-induced vascular endothelial growth factor and collagen IV expression in cultured mesangial cells.罗格列酮可预防高糖诱导的培养系膜细胞中血管内皮生长因子和IV型胶原的表达。
Exp Diabetes Res. 2009;2009:910783. doi: 10.1155/2009/910783. Epub 2009 Jul 7.
7
Icariin attenuates high glucose-induced type IV collagen and fibronectin accumulation in glomerular mesangial cells by inhibiting transforming growth factor-β production and signalling through G protein-coupled oestrogen receptor 1.淫羊藿素通过抑制 G 蛋白偶联雌激素受体 1 抑制转化生长因子-β的产生和信号转导，减轻高糖诱导的肾小球系膜细胞型 IV 胶原和纤维连接蛋白的积累。
Clin Exp Pharmacol Physiol. 2013 Sep;40(9):635-43. doi: 10.1111/1440-1681.12143.
8
Ginkgo biloba extract prevents glucose-induced accumulation of ECM in rat mesangial cells.银杏叶提取物可预防葡萄糖诱导的大鼠系膜细胞中细胞外基质的积累。
Phytother Res. 2009 Apr;23(4):477-85. doi: 10.1002/ptr.2652.
9
Purple corn anthocyanins dampened high-glucose-induced mesangial fibrosis and inflammation: possible renoprotective role in diabetic nephropathy.紫玉米花色苷抑制高糖诱导的系膜纤维化和炎症：在糖尿病肾病中可能具有肾脏保护作用。
J Nutr Biochem. 2012 Apr;23(4):320-31. doi: 10.1016/j.jnutbio.2010.12.008. Epub 2011 May 2.
10
Liraglutide suppresses production of extracellular matrix proteins and ameliorates renal injury of diabetic nephropathy by enhancing Wnt/β-catenin signaling.利拉鲁肽通过增强 Wnt/β-连环蛋白信号通路抑制细胞外基质蛋白的产生，改善糖尿病肾病的肾损伤。
Am J Physiol Renal Physiol. 2020 Sep 1;319(3):F458-F468. doi: 10.1152/ajprenal.00128.2020. Epub 2020 Jul 27.

引用本文的文献

1
Glibenclamide protects against thioacetamide-induced hepatic damage in Wistar rat: investigation on NLRP3, MMP-2, and stellate cell activation.格列本脲可预防 Wistar 大鼠硫代乙酰胺肝损伤：NLRP3、MMP-2 和星状细胞激活的研究。
Naunyn Schmiedebergs Arch Pharmacol. 2018 Nov;391(11):1257-1274. doi: 10.1007/s00210-018-1540-2. Epub 2018 Jul 31.
2
Anti-diabetic treatment regulates pro-fibrotic TGF-β serum levels in type 2 diabetics.抗糖尿病治疗调节 2 型糖尿病患者的促纤维化 TGF-β 血清水平。
Diabetol Metab Syndr. 2013 Aug 31;5(1):48. doi: 10.1186/1758-5996-5-48.

本文引用的文献

1
PAI-1 in tissue fibrosis.组织纤维化中的 PAI-1。
J Cell Physiol. 2012 Feb;227(2):493-507. doi: 10.1002/jcp.22783.
2
Plasminogen activator inhibitor-1 antisense oligodeoxynucleotides abrogate mesangial fibronectin accumulation.纤溶酶原激活物抑制剂-1 反义寡脱氧核苷酸可消除肾小球系膜细胞纤维连接蛋白的蓄积。
Korean J Physiol Pharmacol. 2010 Dec;14(6):385-90. doi: 10.4196/kjpp.2010.14.6.385. Epub 2010 Dec 31.
3
Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion.Ets-2 和 p53 介导 cAMP 诱导的 MMP-2 表达、活性和滋养层细胞侵袭。
Reprod Biol Endocrinol. 2009 Nov 25;7:135. doi: 10.1186/1477-7827-7-135.
4
Cilostazol inhibits high glucose- and angiotensin II-induced type 1 plasminogen activator inhibitor expression in artery wall and neointimal region after vascular injury.西洛他唑抑制血管损伤后动脉壁和内膜新生部位高糖和血管紧张素Ⅱ诱导的 1 型纤溶酶原激活物抑制剂表达。
Atherosclerosis. 2009 Dec;207(2):391-8. doi: 10.1016/j.atherosclerosis.2009.06.016. Epub 2009 Jun 18.
5
PAI-1 and kidney fibrosis.纤溶酶原激活物抑制剂-1与肾纤维化
Front Biosci (Landmark Ed). 2009 Jan 1;14(6):2028-41. doi: 10.2741/3361.
6
Matrix metalloproteinases: their potential role in the pathogenesis of diabetic nephropathy.基质金属蛋白酶：它们在糖尿病肾病发病机制中的潜在作用。
Endocrine. 2009 Feb;35(1):1-10. doi: 10.1007/s12020-008-9114-6. Epub 2008 Oct 30.
7
From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy.从纤维化到硬化：糖尿病肾病中肾小球硬化的机制
Diabetes. 2008 Jun;57(6):1439-45. doi: 10.2337/db08-0061.
8
A PAI-1 mutant, PAI-1R, slows progression of diabetic nephropathy.一种纤溶酶原激活物抑制剂-1（PAI-1）突变体PAI-1R可减缓糖尿病肾病的进展。
J Am Soc Nephrol. 2008 Feb;19(2):329-38. doi: 10.1681/ASN.2007040510. Epub 2008 Jan 23.
9
Effects of long-term elevated glucose on collagen formation by mesangial cells.
Kidney Int. 2007 Nov;72(10):1216-25. doi: 10.1038/sj.ki.5002517. Epub 2007 Aug 29.
10
17beta-Estradiol supplementation reduces tubulointerstitial fibrosis by increasing MMP activity in the diabetic kidney.补充17β-雌二醇可通过增加糖尿病肾脏中的基质金属蛋白酶活性来减轻肾小管间质纤维化。
Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R769-77. doi: 10.1152/ajpregu.00375.2006. Epub 2006 Aug 24.