plasminogen activator inhibitor

プラスミノーゲンアクチベーターインヒビター

WordNet

1. limit, block, or decrease the action or function of; "inhibit the action of the enzyme"; "inhibit the rate of a chemical reaction"
2. control and refrain from showing; of emotions, desires, impulses, or behavior (同)bottle up, suppress
3. limit the range or extent of; "Contact between the young was inhibited by strict social customs"
4. a substance that retards or stops an activity
5. (biology) any agency bringing about activation; a molecule that increases the activity of an enzyme or a protein that increases the production of a gene product in DNA transcription
6. an inactive form of plasmin that occurs in plasma and is converted to plasmin by organic solvents

PrepTutorEJDIC

1. 〈感情・欲望・行動・作用など〉‘を'抑制する / (…しないように)〈人〉‘を'抑制する,妨げる《+『名』+『from』+『名』(do『ing』)》
2. 抑制する人(物) / 化学反応抑制剤

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/16 13:48:00」(JST)

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[Wiki en表示]

Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
PAI-1 in complex with the SMB domain of Vitronectin PDB: 1OC0
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1A7C, 1B3K, 1C5G, 1DB2, 1DVM, 1DVN, 1LJ5, 1OC0, 3CVM, 3EOX, 3PB1, 3Q02, 3Q03, 3R4L, 3UT3, 4AQH, 4G8O, 4G8R, 4IC0, 9PAI
Identifiers
Symbols	SERPINE1 ; PAI; PAI-1; PAI1; PLANH1
External IDs	OMIM: 173360 MGI: 97608 HomoloGene: 68070 ChEMBL: 3475 GeneCards: SERPINE1 Gene
Gene ontology Molecular function • protease binding • serine-type endopeptidase inhibitor activity • receptor binding • protein binding Cellular component • extracellular region • extracellular space • plasma membrane • extracellular matrix • platelet alpha granule lumen • extracellular exosome Biological process • chronological cell aging • angiogenesis • platelet degranulation • transcription, DNA-templated • transcription initiation from RNA polymerase II promoter • transforming growth factor beta receptor signaling pathway • blood coagulation • circadian rhythm • gene expression • regulation of receptor activity • negative regulation of plasminogen activation • negative regulation of endopeptidase activity • negative regulation of smooth muscle cell migration • platelet activation • positive regulation of blood coagulation • negative regulation of blood coagulation • extracellular matrix organization • negative regulation of cell migration • positive regulation of interleukin-8 production • negative regulation of cell adhesion mediated by integrin • positive regulation of leukotriene production involved in inflammatory response • fibrinolysis • positive regulation of angiogenesis • positive regulation of transcription from RNA polymerase II promoter • positive regulation of receptor-mediated endocytosis • positive regulation of inflammatory response • defense response to Gram-negative bacterium • negative regulation of fibrinolysis • negative regulation of vascular wound healing • negative regulation of wound healing • cellular response to lipopolysaccharide • positive regulation of monocyte chemotaxis • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors • negative regulation of smooth muscle cell-matrix adhesion • negative regulation of endothelial cell apoptotic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5054	18787
Ensembl	ENSG00000106366	ENSMUSG00000037411
UniProt	P05121	n/a
RefSeq (mRNA)	NM_000602	NM_008871
RefSeq (protein)	NP_000593	NP_032897
Location (UCSC)	Chr 7: 101.13 – 101.14 Mb	Chr 5: 137.06 – 137.07 Mb
PubMed search	[1]	[2]

Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the SERPINE1 gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis

PAI-1 is a serine protease inhibitor (serpin) that functions as the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and hence fibrinolysis (the physiological breakdown of blood clots). It is a serine protease inhibitor (serpin) protein (SERPINE1).

The other PAI, plasminogen activator inhibitor-2 (PAI-2) is secreted by the placenta and only present in significant amounts during pregnancy. In addition, protease nexin acts as an inhibitor of tPA and urokinase. PAI-1, however, is the main inhibitor of the plasminogen activators.

Genetics

The PAI-1 gene is SERPINE1, located on chromosome 7 (7q21.3-q22). There is a common polymorphism known as 4G/5G in the promoter region. The 5G allele is slightly less transcriptionally active than the 4G.

Function

PAI-1 is mainly produced by the endothelium (cells lining blood vessels), but is also secreted by other tissue types, such as adipose tissue.

PAI-1 inhibits the serine proteases tPA and uPA/urokinase, and hence is an inhibitor of fibrinolysis, the physiological process that degrades blood clots.

PAI-1 inhibits the activity of matrix metalloproteinases, which play a crucial role in invasion of malignant cells across the basal lamina.

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

Role in disease

Congenital deficiency of PAI-1 has been reported; as fibrinolysis is not suppressed adequately, it leads to a hemorrhagic diathesis (a tendency to hemorrhage).

PAI-1 is present in increased levels in various disease states (such as a number of forms of cancer), as well as in obesity and the metabolic syndrome. It has been linked to the increased occurrence of thrombosis in patients with these conditions.

In inflammatory conditions in which fibrin is deposited in tissues, PAI-1 appears to play a significant role in the progression to fibrosis (pathological formation of connective tissue). Presumably, lower PAI levels would lead to less suppression of fibrinolysis and conversely a more rapid degradation of the fibrin.

Angiotensin II increases synthesis of plasminogen activator inhibitor-1, so it accelerates the development of atherosclerosis.

Pharmacology

Tiplaxtinin (PAI-039) is a small molecule inhibitor that is being studied for use in the attenuation of remodeling of blood vessels, a result of arterial hypertension and activation of the renin-angiotensin system.

Interactions

Plasminogen activator inhibitor-1 has been shown to interact with ORM1.

References

Further reading

• Mimuro J (1991). "[Type 1 plasminogen activator inhibitor: its role in biological reactions]". Rinsho Ketsueki 32 (5): 487–9. PMID 1870265. 
• Binder BR, Christ G, Gruber F, Grubic N, Hufnagl P, Krebs M et al. (2002). "Plasminogen activator inhibitor 1: physiological and pathophysiological roles". News Physiol. Sci. 17: 56–61. PMID 11909993. 
• Eddy AA (2002). "Plasminogen activator inhibitor-1 and the kidney". Am. J. Physiol. Renal Physiol. 283 (2): F209–20. doi:10.1152/ajprenal.00032.2002. PMID 12110504. 
• Schroeck F, Arroyo de Prada N, Sperl S, Schmitt M, Viktor M (2003). "Interaction of plasminogen activator inhibitor type-1 (PAI-1) with vitronectin (Vn): mapping the binding sites on PAI-1 and Vn". Biol. Chem. 383 (7–8): 1143–9. doi:10.1515/BC.2002.125. PMID 12437099. 
• Gils A, Declerck PJ (2004). "The structural basis for the pathophysiological relevance of PAI-I in cardiovascular diseases and the development of potential PAI-I inhibitors". Thromb. Haemost. 91 (3): 425–37. doi:10.1160/TH03-12-0764. PMID 14983217. 
• Durand MK, Bødker JS, Christensen A, Dupont DM, Hansen M, Jensen JK et al. (2004). "Plasminogen activator inhibitor-I and tumour growth, invasion, and metastasis". Thromb. Haemost. 91 (3): 438–49. doi:10.1160/TH03-12-0784. PMID 14983218. 
• Harbeck N, Kates RE, Gauger K, Willems A, Kiechle M, Magdolen V et al. (2004). "Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer". Thromb. Haemost. 91 (3): 450–6. doi:10.1160/TH03-12-0798. PMID 14983219. 
• Hertig A, Rondeau E (2004). "Plasminogen activator inhibitor type 1: the two faces of the same coin". Curr. Opin. Nephrol. Hypertens. 13 (1): 39–44. doi:10.1097/00041552-200401000-00006. PMID 15090858. 
• Hoekstra T, Geleijnse JM, Schouten EG, Kluft C (2004). "Plasminogen activator inhibitor-type 1: its plasma determinants and relation with cardiovascular risk". Thromb. Haemost. 91 (5): 861–72. doi:10.1267/THRO04050861. PMID 15116245. 
• Lijnen HR (2005). "Pleiotropic functions of plasminogen activator inhibitor-1". J. Thromb. Haemost. 3 (1): 35–45. doi:10.1111/j.1538-7836.2004.00827.x. PMID 15634264. 
• De Taeye B, Smith LH, Vaughan DE (2005). "Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease". Current Opinion in Pharmacology 5 (2): 149–54. doi:10.1016/j.coph.2005.01.007. PMID 15780823. 
• Dellas C, Loskutoff DJ (2005). "Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease". Thromb. Haemost. 93 (4): 631–40. doi:10.1267/THRO05040631. PMID 15841306. 
• Könsgen D, Mustea A, Lichtenegger W, Sehouli J (2005). "[Role of PAI-1 in gynaecological malignancies]". Zentralblatt für Gynäkologie 127 (3): 125–31. doi:10.1055/s-2005-836407. PMID 15915389. 
• Hermans PW, Hazelzet JA (2007). "Plasminogen activator inhibitor type 1 gene polymorphism and sepsis". Clin. Infect. Dis. 41 Suppl 7: S453–8. doi:10.1086/431996. PMID 16237647. 
• Alessi MC, Poggi M, Juhan-Vague I (2007). "Plasminogen activator inhibitor-1, adipose tissue and insulin resistance". Curr. Opin. Lipidol. 18 (3): 240–5. doi:10.1097/MOL.0b013e32814e6d29. PMID 17495595. 

External links

• The MEROPS online database for peptidases and their inhibitors: I04.020
• Plasminogen Activator Inhibitor 1 at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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• 1. 血栓溶解異常による血栓性および出血性疾患 thrombotic and hemorrhagic disorders due to abnormal fibrinolysis
• 2. 線溶マーカーおよび心血管リスク fibrinolytic markers and cardiovascular risk
• 3. 止血の概要 overview of hemostasis
• 4. 血管内皮機能および血栓溶解療法の基本的メカニズム vascular endothelial function and fundamental mechanisms of fibrinolysis thrombolysis
• 5. 妊娠中の先天性血栓性素因 inherited thrombophilias in pregnancy

English Journal

• Redox control of p53 in the transcriptional regulation of TGF-β1 target genes through SMAD cooperativity.

• Overstreet JM1, Samarakoon R1, Meldrum KK2, Higgins PJ3.
• Cellular signalling.Cell Signal.2014 Jul;26(7):1427-36. doi: 10.1016/j.cellsig.2014.02.017. Epub 2014 Mar 5.
• Transforming growth factor-β1 (TGF-β1) regulates the tissue response to injury and is the principal driver of excessive scarring leading to fibrosis and eventual organ failure. The TGF-β1 effectors SMAD3 and p53 are major contributors to disease progression. While SMAD3 is an established pro-fibr
• PMID 24613410

• The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis.

• Nikolopoulos GK, Bagos PG, Tsangaris I, Tsiara CG, Kopterides P, Vaiopoulos A, Kapsimali V, Bonovas S, Tsantes AE.
• Clinical chemistry and laboratory medicine : CCLM / FESCC.Clin Chem Lab Med.2014 Jul 1;52(7):937-50. doi: 10.1515/cclm-2013-1124.
• Abstract Background: The circulating levels of plasminogen activator inhibitor type 1 (PAI-1) are increased in individuals carrying the 4G allele at position -675 of the PAI-1 gene. In turn, overexpression of PAI-1 has been found to affect both atheroma and thrombosis. However, the association betwe
• PMID 24695040

• Osteopontin promotes the progression of gastric cancer through the NF-κB pathway regulated by the MAPK and PI3K.

• Liu J1, Liu Q2, Wan Y1, Zhao Z1, Yu H3, Luo H3, Tang Z1.
• International journal of oncology.Int J Oncol.2014 Jul;45(1):282-90. doi: 10.3892/ijo.2014.2393. Epub 2014 Apr 17.
• To elucidate the biological functions of osteopontin (OPN) in gastric tumors and to better understand the molecular events of OPN responsible for the malignancy, the present studies were performed. Growth curve, apoptosis assay, invasion assay and migration assay revealed that OPN status significant
• PMID 24756245

Japanese Journal

• 血球貪食症候群に合併したDICにトロンボモデュリンアルファを投与した1症例 : 血漿中プラスミノーゲンアクチベーターインヒビターの消長から

• 矢野 武志,與那覇 哲,田村 隆二 [他]
• ICUとCCU = Japanese journal of intensive care medicine : 集中治療医学 37(1), 75-79, 2013-01
• NAID 40019587057

• 第35回学術集会SPCシンポジウム:PAI-I as a therapeutic target of a prothrombotic state：Insights from a murine model

• 竹下 享典
• 日本血栓止血学会誌 24(5), 516-519, 2013
• NAID 130003384147

• 乳癌の浸潤転移と線溶系因子

• 梅田 朋子,江口 豊
• 日本血栓止血学会誌 24(5), 496-500, 2013
• NAID 130003384144

Related Links

• PAI-1 (プラスミノーゲン活性化抑制因子)

PAI-1 (plasminogen activator inhibitor-1) PAI-1は、組織プラスミノーゲンアクチベーター(t-PA)の活性を消失させ、線溶系を抑制するポリペプチドです。敗血症、動脈硬化等になると高値を示します。 プラスミンは、プラスミノーゲンがt-PA ...

• Plasminogen activator inhibitor-1とは - goo Wikipedia ...

Mimuro J (1991). "[Type 1 plasminogen activator inhibitor: its role in biological reactions]". Rinsho Ketsueki 32 (5): 487–9. PMID 1870265. Binder BR, Christ G, Gruber F, Grubic N, Hufnagl P, Krebs M et al. (2002). "Plasminogen ...

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★リンクテーブル★

リンク元	「プラスミノーゲンアクチベーターインヒビター」「プラスミノーゲンアクチベーターインヒビター2」「プラスミノーゲンアクチベーターインヒビター3」「plasminogen inactivator」「プラスミノゲンアクチベータ・インヒビター」
拡張検索	「plasminogen activator inhibitor 1」「plasminogen activator inhibitors」「plasminogen activator inhibitor 1 deficiency」「plasminogen activator inhibitor-1」
関連記事	「inhibit」「inhibitor」「activator」「plasminogen activator」

「プラスミノーゲンアクチベーターインヒビター」

　　[★]

英

plasminogen activator inhibitor PAI

同

プラスミノーゲン活性化因子阻害薬、プラスミノーゲン活性化因子阻害因子、プラスミノーゲン活性化因子インヒビター、プラスミノゲンアクティベーターインヒビター

プラスミノーゲン活性化因子インヒビター plasminogen activator inhibitor

関

PAI-1, PAI-2

[show details]

プラスミノーゲンアクチベーターインヒビター : 約 42,500 件
プラスミノゲンアクチベーターインヒビター : 約 12,500 件
プラスミノーゲン活性化因子インヒビター : 約 9,050 件
プラスミノゲン活性化因子インヒビター : 60 件

プラスミノーゲンアクチベーターインヒビター PAI : 約 26,500 件
プラスミノゲンアクチベーターインヒビター PAI : 約 8,890 件
プラスミノーゲン活性化因子インヒビター PAI : 約 3,150 件
プラスミノゲン活性化因子インヒビター PAI : 41 件

• 血管内皮細胞が産生
• 過剰なt-PA作用を抑制する

「プラスミノーゲンアクチベーターインヒビター2」

　　[★]

英

plasminogen activator inhibitor 2、PAI-2

同

プラスミノーゲン活性化因子インヒビター2

関

プラスミノーゲンアクチベーターインヒビター plasminogen activator inhibitor PAI

[show details]

プラスミノーゲン活性化因子インヒビター2 : 37 件
プラスミノーゲンアクチベーターインヒビター2 : 20 件

-PAI-2

「プラスミノーゲンアクチベーターインヒビター3」

　　[★]

英

plasminogen activator inhibitor 3、PAI-3

同

プラスミノーゲン活性化因子インヒビター3

関

プラスミノーゲンアクチベーターインヒビター plasminogen activator inhibitor PAI、プロテインCインヒビター

「plasminogen inactivator」

　　[★]

• プラスミノーゲン阻害因子

関

plasminogen activator inhibitor

「プラスミノゲンアクチベータ・インヒビター」

　　[★]

英

plasminogen activator inhibitor PAI

「plasminogen activator inhibitor 1」

　　[★]

プラスミノーゲン活性化因子インヒビター1、プラスミノーゲンアクチベーターインヒビター1

関

PAI-1

「plasminogen activator inhibitors」

　　[★] プラスミノーゲンアクチベーターインヒビター。PAIs

「plasminogen activator inhibitor 1 deficiency」

　　[★] プラスミノゲンアクチベーターインヒビター1欠乏症

「plasminogen activator inhibitor-1」

　　[★] プラスミノゲンアクチベータインヒビター-1

「inhibit」

　　[★]

• v.

• 抑制する、阻害する、阻止する

関

abrogate、block、depress、depression、deter、inhibition、interdict、prevent、prevention、repress、repression、restrain、restraint、suppress、suppression

　 　 　 　

「inhibitor」

　　[★]

• n.

• 阻害剤、阻害薬、抑制薬、抑制剤、(内在性物質について)インヒビター、抑制物質

関

blocker、depressant、suppressant

　 　

「activator」

　　[★]

• n.

• 活性化因子、活性化薬、活性化剤、賦活薬、活性化物質、アクチベーター、アクティベーター

　

「plasminogen activator」

　　[★] プラスミノーゲンアクチベーター, PA