• BMB Reports
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• 제46권11호
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• pp.550-554
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• 2013

The platelet-derived growth factor (PDGF) signaling pathway is essential for inducing a dedifferentiated state of vascular smooth muscle cells (VSMCs). Activation of PDGF inhibits smooth muscle cell (SMC)-specific gene expression and increases the rate of proliferation and migration, leading to dedifferentiation of VSMCs. Recently, microRNAs have been shown to play a critical role in the modulation of the VSMC phenotype in response to extracellular signals. However, little is known about microRNAs regulated by PDGF in VSMCs. Herein, we identify microRNA- 15b (miR-15b) as a mediator of VSMC phenotype regulation upon PDGF signaling. We demonstrate that miR-15b is induced by PDGF in pulmonary artery smooth muscle cells and is critical for PDGF-mediated repression of SMC-specific genes. In addition, we show that miR-15b promotes cell proliferation. These results indicate that PDGF signaling regulates SMC-specific gene expression and cell proliferation by modulating the expression of miR-15b to induce a dedifferentiated state in the VSMCs.

• Journal of Chest Surgery
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• 제10권1호
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• pp.44-48
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• 1977

Benign hyperplasia of hilar lymph glands is rare. Most of the lesions were intrathoracic cavity. The lesions were discovered most often on routine roentgenograms of the chest or because. of pressure symptoms or the presence of a palpable mass if outside the thorax. Diagnosis is. made after removal of gland, a procedure which may also have therapeutic value. They have been divided into 2 histol0gic types: the hyaline-vascular lesions, which were, most numerous, were characterized by small hyaline-vascular follicles and interfollicular capillary proliferation ;the plasma cell lesions were characterized by large follicles with! intervening sheets of plasma cells. We experienced one case of benign hyperplasia of lymph gland in left hilum, which were. most numerous, characterized by small hyaline-vascular follicles and interfollicular capillary proliferation-hyaline-vascular type. This 29 years old male patient was treated by right upper lobectomy with excision of lesion. The postoperative courses was uneventful.

• The Korean Journal of Physiology and Pharmacology
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• 제7권1호
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• pp.25-28
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• 2003

Ion channel inhibitors are widely used for pharmacological discrimination between the different channel types as well as for determination of their functional role. In the present study, we tested the hypothesis that 4-aminopyridine (4-AP) could affect the large conductance $Ca^{2+}$-activated $K^+$ channel ($BK_{Ca}$) currents using perforated-patch or cell-attached configuration of patch-clamp technique in the rabbit pulmonary arterial smooth muscle. Application of 4-AP reversibly inhibited the spontaneous transient outward currents (STOCs). The reversal potential and the sensitivity to charybdotoxin indicated that the STOCs were due to the activation of $BK_{Ca}$. The $BK_{Ca}$ currents were recorded in single channel resolution under the cell-attached mode of patch-clamp technique for minimal perturbation of intracellular environment. Application of 4-AP also inhibited the single $BK_{Ca}$ currents reversibly and dose-dependently. The membrane potential of rabbit pulmonary arterial smooth muscle cells showed spontaneous transient hyperpolarizations (STHPs), presumably due to the STOC activities, which was also inhibited by 4-AP. These results suggest that 4-AP can inhibit $BK_{Ca}$ currentsin the intact rabbit vascular smooth muscle. The use of 4-AP as a selective voltage-dependent $K^+$ (KV) channel blocker in vascular smooth muscle, therefore, must be reevaluated.

• 대한기관식도과학회지
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• 제4권1호
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• pp.112-116
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• 1998

Castleman's disease was originally described as a localized mediastinal lymph node enlargement characterized by angiofollicular hyperplasia and intrafollicular capillary proliferation, with surgical removal of mass the only treatment required. It has been divided into two distict histologic types. The hyaline-vascular type is more common and characterized by small hyaline-vascular follicles and interfollicular proliferation. The plasma-cell type is occurred less frequent and more likely to present with constituitional symptoms. It commonly involves the mediastinal and pulmonary lymph nodes, with neck involvement in only 15% to 20% of cases. We report two cases of hyaline-vascular type of Castleman's disease located in the neck area with references to recent literature.

• IMMUNE NETWORK
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• 제15권4호
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• pp.206-211
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• 2015

Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-${\delta}$ (PKC-${\delta}$) in ALI has been a controversial topic. Here we investigated PKC-${\delta}$ function in ALI using PKC-${\delta}$ knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-${\delta}$ KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-${\delta}$ inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-${\delta}$-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-${\delta}$ inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-${\delta}$ inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils.

• International Journal of Vascular Biomedical Engineering
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• 제4권1호
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• pp.9-16
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• 2006

In this article we introduce computer models that have been developed in the past to determine the concentration of metabolic gases, the oxygen and carbon dioxide, along the pulmonary circulation. The terminal concentration of these gases in the arterial blood is related with the total change of the partial pressure of the same gases in the alveoli for the time beginning with inspiration and ending with expiration. It is affected not only by the ventilation-perfusion ratio and the gas diffusion capacity of the lung membrane but also by the pulmonary defect such as shunt, dead space, diffusion impairment and ventilation-perfusion mismatch. Some pathological pulmonary symptoms such as ARDS and CDPD can be understood through the mathematical models of these pulmonary dysfunctions. Quantitative study on the blood oxygenation process using various computer models is therefore of foremost importance in order to monitor not only the pulmonary health but also the cardiac output and cell metabolism. Reviewed in this paper include the basic and advanced methods that enable numerical study on the gas exchange and on the arterial oxygenation process, which might depend on the various heart and lung physiological conditions listed above.

• Journal of Nutrition and Health
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• 제32권3호
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• pp.318-326
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• 1999

Apoptotic cell death, characterized by DNA fragmentation and morphological changes, has previously been shown to occur in vascular endothelial cells cultured with hydrogen peroxide. The present study examined the induction of apoptosis by hydrogen peroxide and whether pyruvate, a key glycolytic intermediate and $\alpha$-keto-monocarboxylate, can inhibit the apoptotic effects in bovine pulmonary artery endothelial cells(BPAECs). Culture with 500uM hydrogen peroxide resulted in 30% cell death and induced morphological changes and DNA fragmentation. Cell injury was inhibited by the treatment with pyruvate. Pyruvate(0.1-5.0mM), and cell viability increased in a dose-dependent manner. In the presence of pyruvate(10~20mM), the viability was improved to over 95%. In contrast, treatment with lactate, a reduced form of phyuvate, did not protect against cell death oxidative stress-induced loss of viability and apoptosis was examined with $\alpha$-cyano-3-hydroxycinnarmate(COHC) as a selective mitochondrial monocarboxylate transport blocker. Incubation with COHC(500uM) did not significantly affect cell viability in the presence of hydrogen peroxide. The cytoprotection by pyruvate(3mM)against hydrogen peroxide stress was abolished by COHC. This indicates that the cytoprotection by pyruvate against oxidative stress in endothelial cells is mediated, at least in part, by mitochondrial pyruvate uptake and hence endothelial enerygetics. However, cytosolic mechanisms related, at least in part, by mitochondrial pyruvate uptake and hence endothelial energetics. However, cytosolic mechanisms related to the glutathione system may also contribute. The results suggest that pyruvate has therapeutic potential in the treatment of oxidative stress-induced cytotoxicity associated with increased apoptosis.

• BMB Reports
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• 제55권11호
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• pp.565-570
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• 2022

Pulmonary arterial hypertension (PAH) is a progressive and devastating disease whose pathogenesis is associated with a phenotypic switch of pulmonary arterial vascular smooth muscle cells (PASMCs). Bone morphogenetic protein (BMP) signaling and potassium two pore domain channel subfamily K member 3 (KCNK3) play crucial roles in PAH pathogenesis. However, the relationship between BMP signaling and KCNK3 expression in the PASMC phenotypic switching process has not been studied. In this study, we explored the effect of BMPs on KCNK3 expression and the role of KCNK3 in the BMP-mediated PASMC phenotypic switch. Expression levels of BMP receptor 2 (BMPR2) and KCNK3 were downregulated in PASMCs of rats with PAH compared to those in normal controls, implying a possible association between BMP/BMPR2 signaling and KCNK3 expression in the pulmonary vasculature. Treatment with BMP2, BMP4, and BMP7 significantly increased KCNK3 expression in primary human PASMCs (HPASMCs). BMPR2 knockdown and treatment with Smad1/5 signaling inhibitor substantially abrogated the BMP-induced increase in KCNK3 expression, suggesting that KCNK3 expression in HPASMCs is regulated by the canonical BMP-BMPR2-Smad1/5 signaling pathway. Furthermore, KCNK3 knockdown and treatment with a KCNK3 channel blocker completely blocked BMP-mediated anti-proliferation and expression of contractile marker genes in HPAMSCs, suggesting that the expression and functional activity of KCNK3 are required for BMP-mediated acquisition of the quiescent PASMC phenotype. Overall, our findings show a crosstalk between BMP signaling and KCNK3 in regulating the PASMC phenotype, wherein BMPs upregulate KCNK3 expression and KCNK3 then mediates BMP-induced phenotypic switching of PASMCs. Our results indicate that the dysfunction and/or downregulation of BMPR2 and KCNK3 observed in PAH work together to induce aberrant changes in the PASMC phenotype, providing insights into the complex molecular pathogenesis of PAH.

• 대한한방내과학회지
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• 제20권1호
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• pp.83-98
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• 1999

This study is designed to investigate the effects of Samul-Tang extract on the response of lactic dehydrogenase(LDH) release, cellular activity, lipid peroxidation, DNA synthesis and the changes of total protein of bovine pulmonary artery endothelial cells(PAEC) from hydrogen peroxide$(H_2O_2)$-induced injury. The results are as follows : 1. Samul-Tang significantly decreased $H_2O_2$-induced release of LDH from injured bovine PAEC. 2. Samul-Tang significantly repressed $H_2O_2$-induced cellular activity from injured bovine PAEC. 3. Samul-Tang significantly repressed $H_2O_2$-induced lipid peroxidation from injured bovine PAEC. 4. Samul-Tang significantly stimulated DNA synthesis in bovine PAEC. 5. Samul-Tang significantly repressed $H_2O_2$-induced changes of total protein volume from injured bovine PAEC. Above results suggest that Samul-Tang can protect bovine PAEC from $H_2O_2$-induced injury. These results can be effectively applied to the prevention and cure of cardiovascular and cerebrovascular diseases.

• 동의생리병리학회지
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• 제17권1호
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• pp.136-139
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• 2003

Cytotoxicity of glucose oxidase(GO) and cardioprotective effect of Salviae Multiorrhizae Radix(SMR) against GO-induced cardiotoxicity were measured for evaluation of cardiotoxicity on cultured mouse pulmonary endotherial cells(PEC) by MTT assay after PEC were cultured for 8 hours at various concentrations of GO. GO was toxic in a time and dose-dependent manner on cultured PEC after PEC were grown for 8 hours in media containing 1～60mU/ml GO. While, cultures were pretreated with 60 μg/ml SMR for 2 hours increased remarkably cell viability. From the above results, it is suggested that GO is toxic on cultured PEC by the decrease of cell viability, and herb medicine such as SMR is very effective in the prevention of vascular toxicity induced by GO.