SERPINE1，又稱為PAI-1，是一種與血液凝固和纖溶有關(guān)的蛋白質(zhì)。最新研究表明，PAI-1可能與肥胖、代謝綜合征、心血管疾病等疾病的發(fā)生和發(fā)展有關(guān)。同時，PAI-1還被認(rèn)為是一種潛在的治療靶點(diǎn)。

Serine protease inhibitor. Inhibits TMPRSS7. Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots. As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading. Acts as a regulator of cell migration, independently of its role as protease inhibitor. It is required for stimulation of keratinocyte migration during cutaneous injury repair. It is involved in cellular and replicative senescence. Plays a role in alveolar type 2 cells senescence in the lung. Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis.

1. results of study have not shown that individual genetic variation in PAI-1 is an independent variable that predispose same of children for renal scarring after first febrile urinary tract infection PMID: 29736094
2. upregulation of PAI-1 may be a critical mechanism underlying insufficient neurotrophic support and increased neurodegeneration associated with AD. Thus, targeting BDNF maturation through pharmacological inhibition of PAI-1 might become a potential treatment for AD. PMID: 28132883
3. CCL5, from endothelial cells, acts in a paracrine fashion on triple-negative breast cancer (TNBC) cells to enhance their migration, invasion, and metastasis. CCL5, in turn, accelerates TNBC cell secretion of PAI-1 and promotes TNBC cell metastasis, thus forming a positive feedback loop. Moreover, this enhanced metastatic ability is reversible and dependent on CCL5 signaling via the chemokine receptor, CCR5. PMID: 28899878
4. The present study shows that mean serum TSH and PAI-1 levels were higher in MetS cases as compared to healthy controls and even higher in MetS cases with SCH as compared to MetS cases without SCH. Thus, it can be summarized that in MetS with the presence of thyroid dysfunction, adipocytes behave abnormally and secrete various adipokines such as PAI-1 which in future may lead to thrombotic complication PMID: 29261514
5. Protease nexin-1 prevents growth of human B cell lymphoma via inhibition of sonic hedgehog signaling. PMID: 29483508
6. PAI-1 gene polymorphisms have roles in atherosclerotic diseases [review] PMID: 29908999
7. Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study. PMID: 28777103
8. The G-4G-C/A-5G-G PAI-1 haplogenotype may be a genetic marker of susceptibility for obesity and hypertriglyceridemia in Mexican children PMID: 29938477
9. The analysis of genotype coexistence revealed a higher incidence of the combination of the ACE II and the PAI-1 4G/4G genotypes in the control group (10.0 vs.5.9% in control group; p = 0.17). CONCLUSIONS: The obtained results suggest no apparent association between the ACE I/D, PAI-1 4G/5G polymorphisms and increased RM susceptibility in the analyzed Polish population. PMID: 27321098
10. Serum PAI-1 level at the time of traumatic brain injury may serve as a predictive biomarker of late pituitary dysfunction in mild traumatic brain injury patients. PMID: 28931364
11. The personalization of the patients' treatment using uPA/PAI-1 tumor levels allows the reversion of the well-known poor prognostic impact of high uPA/PAI-1 levels and strongly supports the use of this biomarker in clinical practice. PMID: 28685212
12. Data show that plasminogen activator inhibitor-1 (PAI-1) and chemokine CCL5 (CCL5) overexpression promoted cell proliferation and migration in breast cancer cells. PMID: 29601121
13. Multiple sclerosis patients were categorized as not cognitively impaired (NCI) and cognitively impaired (CI). The NCI group had a higher percentage of heterozygous subjects but no statistical differences were found between the CI and NCI group. Neuropsychological functioning did not correlate with plasma levels of PAI-1 or its genetic polymorphism. PAI-1 plasma levels were related to neurological impairment. PMID: 29111023
14. Results demonstrated that EMT could promote the secretion of PAI-1 in the triple negative breast cancer (TNBC) cells. TNBC-secreted PAI-1 could increase cell growth, migration and invasion, and the expression of EMT markers in the TNBC cell lines and xenograft mice model. Most importantly, PAI-1 expression is significantly elevated in the breast cancer tissues and associated with prognosis of patients with TNBC. PMID: 29802992
15. Plasma PAI-1 levels may be determined by the degree of obesity and triglyceride metabolic disorders. These factors correlate with a decreased LDL-particle size, increasing the risk of atherosclerosis. PMID: 28692480
16. In this meta-analysis, it was determined that PAI-1 polymorphism confers a genetic contribution to the development of recurrent spontaneous abortion. PMID: 28395596
17. The A allele and AA genotype of rs6092 in SERPINE 1 may protect against T2 diabetes, and have a protective effect on waist circumference, but a negative effect on Triglycerides in men, while may contribute to a lower HbA1c level in women. PMID: 29627522
18. Adjuvant chemotherapy was 9% less likely to be recommended by a multidisciplinary board when using the current criteria compared with using a combination of the St. Gallen criteria and Ki67 and uPA/PAI-1 status (P = 0.03). Taken together, our data show discordance among markers in identifying the risk of recurrence, even though each marker may prove to be independently valid. PMID: 28954632
19. Study shows that hyperglycaemia-induced repression of miR-30c increases PAI-1 expression and thrombus formation in type 2 diabetic mellitus. PMID: 27819307
20. human plasma protects against endothelial cell apoptosis through sustained BAD phosphorylation, which is achieved by, at least in part, a novel interaction between PP1 with PAI1. PMID: 28296156
21. Statistically significant association was not found between 4G/4G genotype and CVT risk. PAI-1 4G/4G is a strong risk factor for venous thrombosis in Indian patients and should be included in laboratory testing panel of thrombophil. PMID: 28561456
22. PAI-1 -675 4G/5G polymorphism was not associated with type 2 diabetes mellitus risk in this population. PMID: 28838342
23. the association of a gain-of-function polymorphism in the PAI-1 promoter region, rs2227631, with lung function is modified by asthma status. The polymorphism is associated with decreased FEV1/FVC ratio and increased prevalence of airway obstruction in Latino and African American subjects with asthma, but it has no effect in healthy controls. PMID: 28543872
24. Plasminogen activator inhibitor-1 has a role in determining leukocyte telomere length in American Indians PMID: 28378522
25. we have identified a detailed molecular mechanism in which p53 acts in partnership with Smad to selectively enhance PAI-1 transcription. PMID: 27759037
26. PAI-1 is implicated in the pathophysiology of depression. PMID: 27456456
27. Plasminogen activator inhibitor 1 (PAI-1) is associated with the risk of Alzheimer's disease (AD) in Tunisian patients. PMID: 28466654
28. PAI-1 levels are increased in patients with recurrent pregnancy losses (RPL), preeclampsia, intrauterine growth restriction (IUGR), gestational diabetes mellitus (GDM) in the previous pregnancy, endometriosis and polycystic ovary syndrome (PCOS). In general, an increased expression of PAI-1 in the blood is associated with an increased risk for infertility and a worse pregnancy outcome. PMID: 28758928
29. PAI-1/tPA ratio may be an important parameter to monitor the progression of OSMF, and normalizing this ratio to 1:1 may reinstate the normal healing pattern in OSMF cases PMID: 27212010
30. uPA, uPAR, and PAI-1 expression was up-regulated in the epidermis of psoriatic skin and in tumor cells in basal cell carcinomas. PMID: 28429105
31. evidence for the significant association of PAI-1 4G/5G polymorphism with an increased risk of adult but not pediatric ischemic stroke (Meta-Analysis) PMID: 26742513
32. Review/Meta-analysis: indicates a causal effect of elevated PAI-1 level on coronary heart disease risk, which may be mediated by glucose dysfunction. PMID: 28550093
33. Case Report: mutation in a highly conserved glycine residue in strand 5B of plasminogen activator inhibitor 1 causes polymerization and PAI-1 deficiency. PMID: 28229167
34. PAI-1 and TGF-beta1 promote non-small cell lung cancer tumor cells and tumor-associated macrophages and might be valuable targets for cancer immunosuppression. PMID: 29253845
35. This study suggests that PAI-1 is an independent predictor of impaired insulin sensitivity among chronic HIV-infected individuals. PMID: 28322572
36. Our study suggested that SERPINE1 may be a promising therapeutic target for chemoresistance. PMID: 28975405
37. PAI-1 mRNA expression is significantly increased in cutaneous lesions of patients with livedoid vasculopathy lesions. PMID: 28186689
38. We show that the tumor-suppressive actions of MEPs are mediated by PAI-1, uPA and its receptor, uPAR, and are sustained even in the presence of the CAFs, which themselves enhance DCIS tumorigenesis via IL-6 signaling. PMID: 28506312
39. The concentration of tPA/PAI-1 complex is an independent predictor of mortality from all causes and from cardiovascular causes in patients with heart failure and preserved ejection fraction. PMID: 27975104
40. tPA:Ag and PAI-1:Ag concentration analysis in diabetic foot syndrome depending on age, gender and BMI did not show any significant differences PMID: 28193577
41. The homozygous variant 4G/4G also was found to be associated with the higher PAI-1 levels (0.005). The variant allele 4G of PAI-1 4G/5G polymorphism and higher plasma PAI-1 levels were found to be significantly associated with IS in young Asian Indians. PMID: 28460568
42. uPA/uPAR and SERPINE1 have roles in in head and neck cancer tumor resistance, metastasis, prognosis and therapy [review] PMID: 27385000
43. High PAI-1 expression is associated radioresistance and aggressiveness of non-small cell lung cancer. PMID: 27004408
44. The PAI-1 4G/5G genotype was not a relevant predictor of persistent residual venous occlusion after idiopathic deep vein thrombosis, which however was associated with age. PMID: 28347810
45. data suggest that even an isocaloric exchange of macronutrients - for example, a switch to a fat-rich diet - affects PAI-1 concentrations in humans and that this is highly heritable. PMID: 28633683
46. The current study revealed a significant increase level of TAFI and PAI-1, coupled with a decrease in PAI-2 in women with severe preeclampsia in comparison with the control group. PMID: 27598010
47. The abundance of free PAI-1 and TAFI in the plaque may inhibit plasmin generation and thereby counteract plaque destabilization by fibrinolysis, cell migration and inflammation PMID: 28135035
48. Genotype PAI 4G/4G is significantly more common in patients with allergic rhinitis (28.1% vs. 16.1%; P = 0.017) compared to the genotype 5G/5G. The results suggest that the carriers of at least one 4G allele are at a higher risk for developing symptoms of allergic rhinitis in asthma. PMID: 28258374
49. Genetic polymorphism in the promoter region of the PAI-1 gene was associated with early onset coronary artery disease. PMID: 27805237
50. MetS prevalence in the Ghanaian population studied was comparable to that of the industrialized West. PAI-1 may serve as a key link between MetS, as currently defined, and the endpoints with which it is associated. PMID: 27697752

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Plasminogen activator inhibitor-1 deficiency (PAI-1D)

Secreted.

Serpin family

Expressed in endothelial cells. Found in plasma, platelets, and hepatoma and fibrosarcoma cells.

HGNC: 8583

OMIM: 173360

KEGG: hsa:5054

STRING: 9606.ENSP00000223095

UniGene: Hs.414795