• 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

重组 GPI 锚定 TIMP-1 可刺激腹膜间皮细胞的生长和迁移。

Recombinant GPI-anchored TIMP-1 stimulates growth and migration of peritoneal mesothelial cells.

机构信息

Arbeitsgruppe Klinische Biochemie, Medizinische Klinik und Poliklinik IV, Universität München, Munich, Germany.

出版信息

PLoS One. 2012;7(4):e33963. doi: 10.1371/journal.pone.0033963. Epub 2012 Apr 27.

DOI:10.1371/journal.pone.0033963
PMID:22558080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3338742/
Abstract

BACKGROUND

Mesothelial cells are critical in the pathogenesis of post-surgical intraabdominal adhesions as well as in the deterioration of the peritoneal membrane associated with long-term peritoneal dialysis. Mesothelial denudation is a pathophysiolocigally important finding in these processes. Matrix metalloproteinase (MMP) biology underlies aspects of mesothelial homeostasis as well as wound repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) moderate MMP activity.

METHODS AND FINDING

By modifying human TIMP-1 through the addition of a glycosylphosphatidylinositol (GPI) anchor, a recombinant protein was generated that efficiently focuses TIMP-1 on the cell surface. Treatment of primary mesothelial cells with TIMP-1-GPI facilitates their mobilization and migration leading to a dramatic increase in the rate of wound experimental closure. Mesothelial cells treated with TIMP-1-GPI showed a dose dependent increase in cell proliferation, reduced secretion of MMP-2, MMP-9, TNF-α and urokinase-type plasminogen activator (uPA), but increased tissue plasminogen activator (t-PA). Treatment resulted in reduced expression and processing of latent TGF-β1.

CONCLUSIONS

TIMP-1-GPI stimulated rapid and efficient in vitro wound closure. The agent enhanced mesothelial cell proliferation and migration and was bioactive in the nanogram range. The application of TIMP-1-GPI may represent a new approach for limiting or repairing damaged mesothelium.

摘要

背景

间皮细胞在术后腹腔粘连的发病机制以及与长期腹膜透析相关的腹膜膜恶化中起着至关重要的作用。间皮细胞剥脱是这些过程中病理生理学上的重要发现。基质金属蛋白酶（MMP）生物学是间皮稳态和伤口修复的基础。内源性金属蛋白酶组织抑制剂（TIMPs）调节 MMP 活性。

方法和发现

通过在人 TIMP-1 上添加糖基磷脂酰肌醇（GPI）锚，生成了一种重组蛋白，可有效地将 TIMP-1 聚焦在细胞表面。用 TIMP-1-GPI 处理原代间皮细胞可促进其动员和迁移，从而显著增加伤口实验闭合的速度。用 TIMP-1-GPI 处理的间皮细胞表现出细胞增殖的剂量依赖性增加，MMP-2、MMP-9、TNF-α 和尿激酶型纤溶酶原激活物（uPA）的分泌减少，但组织型纤溶酶原激活物（t-PA）增加。治疗导致潜伏 TGF-β1 的表达和加工减少。

结论

TIMP-1-GPI 刺激了快速有效的体外伤口闭合。该药物增强了间皮细胞的增殖和迁移活性，并且在纳克范围内具有生物活性。TIMP-1-GPI 的应用可能代表了一种限制或修复受损间皮的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/f4ff12be534c/pone.0033963.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/5b304d2b25b7/pone.0033963.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/448c69f77168/pone.0033963.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/4c1d7beb27c4/pone.0033963.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/37c9476cc6ba/pone.0033963.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/cdcd49149c30/pone.0033963.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/064f1359e1d2/pone.0033963.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/086f23a451be/pone.0033963.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/f4ff12be534c/pone.0033963.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/5b304d2b25b7/pone.0033963.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/448c69f77168/pone.0033963.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/4c1d7beb27c4/pone.0033963.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/37c9476cc6ba/pone.0033963.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/cdcd49149c30/pone.0033963.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/064f1359e1d2/pone.0033963.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/086f23a451be/pone.0033963.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c2/3338742/f4ff12be534c/pone.0033963.g008.jpg

相似文献

1
Recombinant GPI-anchored TIMP-1 stimulates growth and migration of peritoneal mesothelial cells.重组 GPI 锚定 TIMP-1 可刺激腹膜间皮细胞的生长和迁移。
PLoS One. 2012;7(4):e33963. doi: 10.1371/journal.pone.0033963. Epub 2012 Apr 27.
2
Cell surface engineering using glycosylphosphatidylinositol anchored tissue inhibitor of matrix metalloproteinase-1 stimulates cutaneous wound healing.利用糖基磷脂酰肌醇锚定的基质金属蛋白酶-1 组织抑制剂进行细胞表面工程可刺激皮肤伤口愈合。
Wound Repair Regen. 2014 Jan-Feb;22(1):70-6. doi: 10.1111/wrr.12132.
3
Exogenously added GPI-anchored tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) displays enhanced and novel biological activities.外源性添加的糖基磷脂酰肌醇锚定基质金属蛋白酶-1组织抑制剂（TIMP-1）表现出增强的和新的生物学活性。
Biol Chem. 2004 Jul;385(7):655-63. doi: 10.1515/BC.2004.081.
4
Gene transfer of the urokinase-type plasminogen activator receptor-targeted matrix metalloproteinase inhibitor TIMP-1.ATF suppresses neointima formation more efficiently than tissue inhibitor of metalloproteinase-1.靶向尿激酶型纤溶酶原激活物受体的基质金属蛋白酶抑制剂TIMP-1.ATF的基因转移比金属蛋白酶组织抑制剂-1更有效地抑制新生内膜形成。
Circ Res. 2002 Nov 15;91(10):945-52. doi: 10.1161/01.res.0000041418.51906.57.
5
Transforming growth factor-beta1 produced by ovarian cancer cell line HRA stimulates attachment and invasion through an up-regulation of plasminogen activator inhibitor type-1 in human peritoneal mesothelial cells.卵巢癌细胞系HRA产生的转化生长因子-β1通过上调人腹膜间皮细胞中1型纤溶酶原激活物抑制剂来刺激黏附和侵袭。
J Biol Chem. 2003 Jul 18;278(29):26793-802. doi: 10.1074/jbc.M212187200. Epub 2003 May 12.
6
Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer.尿激酶型纤溶酶原激活剂和基质金属蛋白酶在人结直肠癌中的活性与表达
BMC Cancer. 2006 Aug 18;6:211. doi: 10.1186/1471-2407-6-211.
7
Transforming growth factor-beta1 induces tissue inhibitor of metalloproteinase-1 expression via activation of extracellular signal-regulated kinase and Sp1 in human fibrosarcoma cells.转化生长因子-β1通过激活人纤维肉瘤细胞中的细胞外信号调节激酶和Sp1诱导金属蛋白酶组织抑制剂-1表达。
Mol Cancer Res. 2006 Mar;4(3):209-20. doi: 10.1158/1541-7786.MCR-05-0140.
8
ERK1/2 and p38 MAP kinase control MMP-2, MT1-MMP, and TIMP action and affect cell migration: a comparison between mesothelioma and mesothelial cells.细胞外信号调节激酶1/2（ERK1/2）和p38丝裂原活化蛋白激酶（MAP激酶）控制基质金属蛋白酶-2（MMP-2）、膜型基质金属蛋白酶-1（MT1-MMP）和金属蛋白酶组织抑制因子（TIMP）的作用并影响细胞迁移：间皮瘤与间皮细胞的比较
J Cell Physiol. 2006 May;207(2):540-52. doi: 10.1002/jcp.20605.
9
Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in mesothelial cells and their regulation by transforming growth factor-beta1.间皮细胞中基质金属蛋白酶及其组织抑制剂的表达以及它们受转化生长因子-β1的调节
Wound Repair Regen. 1999 Nov-Dec;7(6):477-85. doi: 10.1046/j.1524-475x.1999.00477.x.
10
Urokinase plasminogen activator stimulates function of active forms of stromelysin and gelatinases (MMP-2 and MMP-9) in cirrhotic tissue.尿激酶型纤溶酶原激活剂可刺激肝硬化组织中基质溶解素和明胶酶（MMP-2和MMP-9）活性形式的功能。
J Gastroenterol Hepatol. 2006 Oct;21(10):1544-54. doi: 10.1111/j.1440-1746.2006.04398.x.

引用本文的文献

1
Transfer of Proteins from Cultured Human Adipose to Blood Cells and Induction of Anabolic Phenotype Are Controlled by Serum, Insulin and Sulfonylurea Drugs.血清、胰岛素和磺酰脲类药物控制着从培养的人脂肪细胞向血细胞转移蛋白质和诱导合成代谢表型。
Int J Mol Sci. 2023 Mar 2;24(5):4825. doi: 10.3390/ijms24054825.
2
Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression.肿瘤衍生的白细胞介素 35 通过诱导 ICAM1 的表达促进胰腺导管腺癌细胞的渗出和转移。
Nat Commun. 2017 Jan 19;8:14035. doi: 10.1038/ncomms14035.
3
Targeting matrix metalloproteinases in heart disease: lessons from endogenous inhibitors.

本文引用的文献

1
Blocking TGF-β1 protects the peritoneal membrane from dialysate-induced damage.阻断 TGF-β1 可保护腹膜免受透析液损伤。
J Am Soc Nephrol. 2011 Sep;22(9):1682-95. doi: 10.1681/ASN.2010111197. Epub 2011 Jul 8.
2
Human peritoneal mesothelial cell transformation into myofibroblasts in response to TGF-ß1 in vitro.人腹膜间皮细胞在 TGF-ß1 刺激下体外向肌成纤维细胞的转化。
Int J Mol Med. 2011 Feb;27(2):187-93. doi: 10.3892/ijmm.2010.574. Epub 2010 Dec 6.
3
The mesothelium under the siege of dialysis solutions: old glucose, new glucose, and glucose-free osmotic agents.
靶向治疗心脏病中的基质金属蛋白酶：内源性抑制剂的启示。
Biochem Pharmacol. 2014 Jul 1;90(1):7-15. doi: 10.1016/j.bcp.2014.04.011. Epub 2014 Apr 26.
4
Resident progenitors, not exogenous migratory cells, generate the majority of visceral mesothelium in organogenesis.在器官发生过程中，祖细胞（而非外源性迁移细胞）生成大部分内脏中胚层。
Dev Biol. 2014 Jul 15;391(2):125-32. doi: 10.1016/j.ydbio.2014.04.003. Epub 2014 Apr 16.
5
Recombinant TIMP-1-GPI inhibits growth of fibrosarcoma and enhances tumor sensitivity to doxorubicin.重组组织金属蛋白酶抑制剂-1-糖基磷脂酰肌醇抑制纤维肉瘤生长并增强肿瘤对阿霉素的敏感性。
Target Oncol. 2014 Sep;9(3):251-61. doi: 10.1007/s11523-013-0294-5. Epub 2013 Aug 10.
透析液围攻下的间皮：旧葡萄糖、新葡萄糖及无糖渗透剂
Adv Perit Dial. 2009;25:6-10.
4
Matrix metalloproteinase proteomics: substrates, targets, and therapy.基质金属蛋白酶蛋白质组学：底物、靶点与治疗
Curr Opin Cell Biol. 2009 Oct;21(5):645-53. doi: 10.1016/j.ceb.2009.06.006. Epub 2009 Jul 16.
5
Peritumoral administration of GPI-anchored TIMP-1 inhibits colon carcinoma growth in Rag-2 gamma chain-deficient mice.在Rag-2γ链缺陷小鼠中，肿瘤周围给予糖基磷脂酰肌醇锚定的金属蛋白酶组织抑制因子-1可抑制结肠癌生长。
Biol Chem. 2009 Sep;390(9):893-7. doi: 10.1515/BC.2009.098.
6
Role of viral receptors TLR3, RIG-I and MDA5 in mesothelial tissue-type plasminogen activator and plasminogen activator inhibitor-1 synthesis.病毒受体 TLR3、RIG-I 和 MDA5 在间皮组织型纤溶酶原激活物和纤溶酶原激活物抑制剂-1 合成中的作用。
Thromb Haemost. 2009 Jun;101(6):1128-37. doi: 10.1160/th08-11-0744.
7
Intrinsic cells: mesothelial cells -- central players in regulating inflammation and resolution.固有细胞：间皮细胞——调节炎症和炎症消退的核心参与者。
Perit Dial Int. 2009 Feb;29 Suppl 2:S21-7.
8
TIMP-1-GPI in combination with hyperthermic treatment of melanoma increases sensitivity to FAS-mediated apoptosis.TIMP-1-GPI与黑色素瘤热疗联合使用可增强对FAS介导的细胞凋亡的敏感性。
Cancer Immunol Immunother. 2009 Mar;58(3):361-71. doi: 10.1007/s00262-008-0559-5. Epub 2008 Jul 11.
9
High glucose decreases collagenase expression and increases TIMP expression in cultured human peritoneal mesothelial cells.高糖降低培养的人腹膜间皮细胞中胶原酶的表达并增加金属蛋白酶组织抑制因子的表达。
Nephrol Dial Transplant. 2008 Feb;23(2):534-41. doi: 10.1093/ndt/gfm553. Epub 2007 Nov 23.
10
Regulation of angiogenesis: wound healing as a model.血管生成的调节：以伤口愈合为模型
Prog Histochem Cytochem. 2007;42(3):115-70. doi: 10.1016/j.proghi.2007.06.001. Epub 2007 Aug 20.