• Clinical and Experimental Pediatrics
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• v.50 no.6
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• pp.570-575
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• 2007

Purpose : To demonstrate genetic background of pathogenesis of Kawasaki disease (KD), I examined the genetic polymorphism of plasminogen activator inhibitor-1 (PAI-1) in KD patients. Methods : PCR-RFLP of PAI- 1 promotor gene was analyzed in 56 KD patients admitted to Kyunghee University Hospital, Gachon Medical School Gil Hospital, and Eulji Hospital from March to August 2000 and 206 normal control populations. Results : There were no differences in the genotype and allelic frequency of the PAI-1-675 (4G/5G) and PAI-1-844 (G/A) polymorphic site (which are located in the promoter region) between KD and control subjects. Also I could not detect any significant differences in specific genotypes between patients with the coronary artery lesion (CAL) and patients without CAL. Conclusion : No association was observed in -844 G/A and -675 4G/5G of PAI-1 gene polymorphism with KD.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.107-113
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• 2013

Plasminogen activator inhibitor-1 (PAI-1) is a member of serine protease inhibitor family, which regulates the activity of tissue plasminogen activator (tPA). In CNS, tPA/PAI-1 activity is involved in the regulation of a variety of cellular processes such as neuronal development, synaptic plasticity and cell survival. To gain a more insights into the regulatory mechanism modulating tPA/PAI-1 activity in brain, we investigated the effects of proteasome inhibitors on tPA/PAI-1 expression and activity in rat primary astrocytes, the major cell type expressing both tPA and PAI-1. We found that submicromolar concentration of MG132, a cell permeable peptide-aldehyde inhibitor of ubiquitin proteasome pathway selectively upregulates PAI-1 expression. Upregulation of PAI-1 mRNA as well as increased PAI-1 promoter reporter activity suggested that MG132 transcriptionally increased PAI-1 expression. The induction of PAI-1 downregulated tPA activity in rat primary astrocytes. Another proteasome inhibitor lactacystin similarly increased the expression of PAI-1 in rat primary astrocytes. MG132 activated MAPK pathways as well as PI3K/Akt pathways. Inhibitors of these signaling pathways reduced MG132-mediated upregulation of PAI-1 in varying degrees and most prominent effects were observed with SB203580, a p38 MAPK pathway inhibitor. The regulation of tPA/PAI-1 activity by proteasome inhibitor in rat primary astrocytes may underlie the observed CNS effects of MG132 such as neuroprotection.

• Journal of Life Science
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• v.19 no.10
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• pp.1438-1443
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• 2009

Renal fibrosis is a final common manifestation of every type of chronic kidney disease. Plasminogen activator inhibitor (PAI)-1 is induced by lipopolysaccharide (LPS) and is known to play an essential role in the progress of renal fibrosis. In this paper, we found that an isoprenoid antibiotic, ascofuranone (AF), suppresses expression of profibrotic factors, PAI-1 and promoter activity of PAI-1 induced by LPS in rat kidney fibroblast cells. We therefore investigated signaling pathway mediated inhibitory effects of LPS-induced PAI-1 by AF in rNRK-49F cells. PAI-1 expression is suppressed by treatment with kinase inhibitors for MEK-1/2, as it isin inhibition of PAI-1 expression by AF, and AF inhibits phosphorylation of ERK-1/2. This study suggest that AF suppresses expression of PAI-1 through the inhibition of an ERK-1/2-dependent signal transduction pathway. The data indicates the possibility that AF can be used to prevent the development and progression of renal fibrosis.

• Tuberculosis and Respiratory Diseases
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• v.70 no.6
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• pp.462-473
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• 2011

Background: Smoking is a risk factor for idiopathic pulmonary fibrosis (IPF), but the mechanism of the association remains obscure. There is evidence demonstrating that plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. This study was to determine whether the administration of small interfering RNA (siRNA) targeting PAI-1 or PAI-1 inhibitor to the cigarette smoking extract (CSE)-exposed rat alveolar type II epithelial cells (ATII cells) limits the epithelial-mesenchymal transition (EMT). Methods: ATII cells were isolated from lung of SD-rat using percoll gradient method and cultured with 5% CSE. The EMT was determined from the ATII cells by measuring the real-time RT PCR and western blotting after the PAI-1 siRNA transfection to the cells and after administration of tiplaxtinin, an inhibitor of PAI-1. The effect of PAI-1 inhibitor was also evaluated in the bleomycin-induced rats. Results: PAI-1 was overexpressed in the smoking exposed ATII cells and was directly associated with EMT. The EMT from the ATII cells was suppressed by PAI-1 siRNA transfection or administration of tiplaxtinin. Signaling pathways for EMT by smoking extract were through the phosphorylation of SMAD2 and ERK1/2, and finally Snail expression. Tiplaxtinin also suppressed the pulmonary fibrosis and PAI-1 expression in the bleomycin-induced rats. Conclusion: Our data shows that CSE induces rat ATII cells to undergo EMT by PAI-1 via SMAD2-ERK1/2-Snail activation. This suppression of EMT by PAI-1 siRNA transfection or PAI-1 inhibitor in primary type II alveolar epithelial cells might be involved in the attenuation of bleomycin-induced pulmonary fibrosis in rats.

• Development and Reproduction
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• v.9 no.1
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• pp.43-48
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• 2005

Bone marrow stromal cells, a constituent of the niche for hematopoietic stem cells in bone marrow, provide various factors involved in the fate decision of the hematopoietic stem and progenitor cells. Radiation, a widely used anti-cancer therapy, provokes side effects including the damage of the blood cells. Therefore, it is necessary to recover the blood cells shortly after radiation via promoting the differentiation of hematopoietic cells. In this study, we screened genes modulated by radiation in human bone marrow stromal cells in order to understand the mechanism involved in hematopoiesis after radiation. We performed differential display method by using polymerase chain reaction(PCR) and agarose gel electrophoresis. We found plasminogen activator inhibitor-1(PAI-1) was consistently induced by radiation. The significance of the PAI-1 gene modulation is to be determined.

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.26-32
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• 2004

Purpose : Hypercoagulability is present in patients with nephrotic syndrome. Plasminogen activator inhibitor type 1(PAI-1) is a major inhibitor of plasminogen activators. PAI-1 inactivates both tissue plasminogen activator(tPA) and urokinase plasminogen activator(uPA) by rapid formation of inactive 1:1 stoichiometric complexes. Recently some studies showed that the enhanced PAI-1 expression may be involved in the intraglomerular fibrinogen/fibrinrelated antigen deposition seen in nephrotic syndrome. Methods : PAI-1 gene promoter -844(G/A) polymorphism was evaluated in 146 children with minimal change nephrotic syndrome(MCNS) and 230 control subjects. The patients with MCNS were subdivided into 85 infrequent-relapser(IR) group and 61 frequent relapser(FR) group. PCR of PAI-1 gene promoter region including -844(G/A) and RFLP using the restriction enzyme Xhol were performed for each DNA samples extracted from the groups. Results : The distribution of PAI-1 genotype in the control group was G/G 81(32.5%), A/A 42(16.9%), and G/A 126(50.6%). The distribution of PAI-1 genotypes in the IR group of MCNS was G/G 29(34.1%), A/A 15(17.7%), and G/A 41(48.2%). The distribution of PAI-1 genotype in the FR group of MCNS was G/G 17(27.9%), A/A 18(29.5%), and G/A 26(42.6%). There was a significantly increased frequency of A/A genotype(P=0.0251) in the FR group of MCNS. Conclusion : Our results indicate that the PAI-1 gene promoter A/A genotype may be associated with the FR in MCNS.

• Journal of Ginseng Research
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• v.37 no.4
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• pp.401-412
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• 2013

Korean Red Ginseng (KRG) is an oriental herbal preparation obtained from Panax ginseng Meyer (Araliaceae). To expand our understanding of the action of KRG on central nervous system (CNS) function, we examined the effects of KRG on tissue plasminogen activator (tPA)/plasminogen activator inhibitor-1 (PAI-1) expression in rat primary astrocytes. KRG extract was treated in cultured rat primary astrocytes and neuron in a concentration range of 0.1 to 1.0 mg/mL and the expression of functional tPA/PAI-1 was examined by casein zymography, Western blot and reverse transcription-polymerase chain reaction. KRG extracts increased PAI-1 expression in rat primary astrocytes in a concentration dependent manner (0.1 to 1.0 mg/mL) without affecting the expression of tPA itself. Treatment of 1.0 mg/mL KRG increased PAI-1 protein expression in rat primary astrocytes to $319.3{\pm}65.9%$ as compared with control. The increased PAI-1 expression mediated the overall decrease in tPA activity in rat primary astrocytes. Due to the lack of PAI-1 expression in neuron, KRG did not affect tPA activity in neuron. KRG treatment induced a concentration dependent activation of PI3K, p38, ERK1/2, and JNK in rat primary astrocytes and treatment of PI3K or MAPK inhibitors such as LY294002, U0126, SB203580, and SP600125 (10 ${\mu}M$ each), significantly inhibited 1.0 mg/mL KRG-induced expression of PAI-1 and down-regulation of tPA activity in rat primary astrocytes. Furthermore, compound K but not other ginsenosides such as Rb1 and Rg1 induced PAI-1 expression. KRG-induced up-regulation of PAI-1 in astrocytes may play important role in the regulation of overall tPA activity in brain, which might underlie some of the beneficial effects of KRG on CNS such as neuroprotection in ischemia and brain damaging condition as well as prevention or recovery from addiction.

• Reproductive and Developmental Biology
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• v.33 no.4
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• pp.203-209
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• 2009

The present study was performed to identify changes of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) in porcine oviduct epithelial cells (POECs) during the estrous cycle. POECs obtained from ovary in pre-ovulatory (Pre-Ov), early to mid-luteal stage (Early-mid L) and post-ovulatory stage (Post-Ov). For the examine of PA activity, $1{\times}10^5$ fresh cells of POECs were cultured in DMEM/Ham F-12 containing 10% FBS and 0.2% amphotericin under humidified atmosphere of 5% $CO_2$ in air and $38^{\circ}C$. The urokinase-type PA (uPA) was observed at 7 days of POECs culture. PA activity was measured with culture prolonged of 0, 3, 6, 12 and 24 h after culture of 7 days. The PA activity were high significantly (p<0.05) at 12 h of culture, but PA activity were decreased with culture periods increased. The PA activity in POECs of Post-Ov stage were higher significantly (p<0.05) than that of Early-mid L and Pre-Ov stage. When PAI-1 and PAI-2 were added during the POECs culture, the PA were observed significant low activity (p<0.05). The PA activity and protein expression were decreased by PA inhibitor. This results suggest that PAI-1 and PAI-2 have a suppressive action on change of PA activity during the estrous cycle of pigs. Specifically, this study using PA inhibitor was effect the PA activity and PAI expression in oviduct epithelial cells in pigs.

• Preventive Nutrition and Food Science
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• v.9 no.4
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• pp.336-341
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• 2004

Leptin, resisitn and PAI-1 (plasminogen activator inhibitor-1) are synthesized and secreted by rodent fat cells and recently postulated to be an important link to obesity. This study was conducted to characterize the hormonal regulation of leptin, resistin, and PAI-1 gene expression in the 3T3-L1 adipocytes. The cells were treated with 0.5 $\mu$M insulin, 1 $\mu$M dexamethasone (Dex), or 0.05 $\mu$M triiodothyronine (T3) for 72 hours. The mRNA levels of each peptide were measured by semi-quantitative RT-PCR. The mRNA level of the leptin-producing ob gene was significantly increased by insulin, Dex, and T3 by 3.2-, 3.1- and 2.7-fold, respectively, compared to the control (p < 0.05). The level of resistin mRNA was increased by insulin, Dex, and T3 by 2.7-, 2.5- and 2-fold, respectively, compared to the control (p < 0.05). Likewise, the level of PAI-1 mRNA was significantly increased by insulin, Dex, and T3 compared to the control (p < 0.05). Taken together, our results suggest that insulin, Dex, and T3 may regulate the gene expression of leptin, resistin, and PAI-1 in 3T3-L1 adipocytes.

• Development and Reproduction
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• v.3 no.1
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• pp.29-38
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• 1999

The pathogenesis of endometriosis is unknown, but retrograde menstruation is widely accepted as an etiology. Refluxed endometrium from endometriosis patients is more prone to implant and invade peritoneum possibly through the action of extracellular proteolysis. This proteolytic action may involve plasminogen activators and the collagenase system. Plasminogen activators (PAs) and matrix metalloproteinases (MMPs) play a critical role in the breakdown of extracellular matrix components and basement membrane in the processes of implantation and tumor invasion. PAs are inhibited by plasminogen activator inhibitor (PAI) and MMPs activity is inhibited by tissue inhibitor of metalloproteinase (TIMP). To test the hypothesis that lower expression of PAI-1 and TIMP-3 in endometrium from women with endometriosis, we investigated their PAI-1 and TIMP-3 expression by quantitative competitive RT PCR in endometrium from women with and without endometriosis. Endometrial tissues were obtained from 14 patients with severe endometriosis and 14 patients without endometriosis. Total RNA was extracted and reverse transcribed into cDNA, and quantitative competitive PCR (QC PCR) was performed to evaluate PAI-1 and TIMP-3 mRNA expression. Endometrium from patients with endometriosis showed decreased expression of PAI-1 and TIMP-3 mRNA compared to endometrium from control in luteal phase (p<0.05). Our results suggest that endometrium from women with endometriosis expresses lower levels of PAI-1 and TIMP-3 than endometrium from normal women. Endometrium from endometriosis patients may be more invasive and prone to peritoneal implantation than control because of higher PA and MMP enzymatic activity. Thus, increased proteolytic activity may be one of the reasons for the invasive properties of the endometrium resulting in the development of endometriosis.