• Title/Summary/Keyword: Smooth muscle cell

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Induction of Apoptosis and Its Mechanism by Siegesbeckia Glabrescens in HepG2 cells (간암 세포주에서의 희렴의 Apoptosis 유도와 기전)

  • Kim, Yoon-Tae;Lee, Heon-Jae;Kim, Gil-Whon;Shin, Heung-Mook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.3
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    • pp.640-646
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    • 2005
  • This study was performed for the investigation of anticancer effects of Siegesbeckia glabrescens(SG) on HepG2 cells, a human hepatoma cell line. In the previous study, we examined the involvement of nitric oxide (NO) on anti-proliferative and apoptotic efficacy of SG in vascular smooth muscle cells. The possible mechanism of the apoptotic effects of SG was investigated in HepG2 cells. SG showed potent cytotoxic activity in HepG2 but not chang cells, liver normal cells. SG treatment caused morphological change such as cell shrinkage, nuclei condensation and cell blebbing in HepG2 cells. SG also increased the nitrite production of HepG2 cells in a dose-dependent manner. Furthermore, L-NNA treatment inhibited the anti-proliferative effect of SG. From RT-PCR, SG decreased Bcl-2 but no affected on Bax. Western blot for procaspase-3 and COX-2 showed that degradation of procaspase-3 protein level or inhibition of COX-2 protein expression by SG treatment. In addition, the apoptotic effect of SG was also demonstrated by DNA laddering. In conclusion, SG-induced HepG2 cells death can occur via apoptosis which was dose-dependent, and associated with apoptosis-related Bcl-2/Bax gene expressions, COX-2 inhibition, caspase-3 activation and NO pathway. These results suggest that SG is potentially useful as a chemotherapeutic/chemopreventive agent in hepatocellular carcinoma.

Development of Mechanically Expanded Gelatin-AAc-PLLA/PLCL Nanofibers for Vascular Tissue Engineering by Radiation-based Techniques (방사선 기반에 의한 기계적으로 공극을 증가시킨 젤라틴이 도입된 혈관조직공학용 PLLA/PLCL 나노섬유 지지체의 개발)

  • Jeong, Jin-Oh;Jeong, Sung In;Seo, Da-Eun;Park, Jong-Seok;Gwon, Hui-Jeong;Ahn, Sung-Jun;Shin, Young Min;Lim, Youn-Mook
    • Journal of Radiation Industry
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    • v.9 no.4
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    • pp.171-180
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    • 2015
  • Vascular tissue engineering has been accessed to mimic the natural composition of the blood vessel containing intima, media, and adventitia layers. We fabricated mechanically expanded PLLA/PLCL nanofibers using electrospinning and UTM. The pore size of the meshes was increased the gelatin immobilized AAc-PLLA/PLCL nanofibers ($203.30{\pm}49.62microns$) than PLLA/PLCL nanofibers ($59.99{\pm}8.66microns$) after mechanical expansion. To increase the cell adhesion and proliferation, we introduced carboxyl group, and gelatin was conjugated on them. The properties of the PLLA/PLCL nanofibers were analyzed with SEM, ATR-FTIR, TBO staining, and water contact angle measurement, general cell responses on the PLLA/PLCL nanofibers such as adhesion, proliferation, and infiltration were also investigated using smooth muscle cell (SMC). During the SMC culture, the initial viability of the cells was significantly increased on the gelatin immobilized AAc-PLLA/PLCL nanofibers, and infiltration of the cells was also enhanced on them. Therefore, gelatin immobilized AAc-PLLA/PLCL nanofibers and mechanically expanded meshes may be a good tool for vascular tissue engineering application.

Protective effect and mechanism of ginsenoside Rg2 on atherosclerosis

  • Qianqian Xue;Tao Yu;Zhibin Wang;Xiuxiu Fu;Xiaoxin Li;Lu Zou;Min Li;Jae Youl Cho;Yanyan Yang
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.237-245
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    • 2023
  • Background: Ginsenoside Rg2 (Rg2) has a variety of pharmacological activities and provides benefits during inflammation, cancer, and other diseases. However, there are no reports about the relationship between Rg2 and atherosclerosis. Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to detect the cell viability of Rg2 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). The expression of inflammatory factors in HUVECs and the expression of phenotypic transformation-related marker in VSMCs were detected at mRNA levels. Western blot method was used to detect the expression of inflammation pathways and the expression of phenotypic transformation at the protein levels. The rat carotid balloon injury model was performed to explore the effect of Rg2 on inflammation and phenotypic transformation in vivo. Results: Rg2 decreased the expression of inflammatory factors induced by lipopolysaccharide in HUVECs-without affecting cell viability. These events depend on the blocking regulation of NF-κB and p-ERK signaling pathway. In VSMCs, Rg2 can inhibit the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet derived growth factor-BB (PDGF-BB)-which may contribute to its anti-atherosclerotic role. In rats with carotid balloon injury, Rg2 can reduce intimal proliferation after injury, regulate the inflammatory pathway to reduce inflammatory response, and also suppress the phenotypic transformation of VSMCs. Conclusion: These results suggest that Rg2 can exert its anti-atherosclerotic effect at the cellular level and animal level, which provides a more sufficient basis for ginseng as a functional dietary regulator.

Ginsenoside Rg1 alleviates vascular remodeling in hypoxia-induced pulmonary hypertension mice through the calpain-1/STAT3 signaling pathway

  • Chenyang Ran;Meili Lu;Fang Zhao;Yi Hao;Xinyu Guo;Yunhan Li;Yuhong Su;Hongxin Wang
    • Journal of Ginseng Research
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    • v.48 no.4
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    • pp.405-416
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    • 2024
  • Background: Hypoxic pulmonary hypertension (HPH) is the main pathological change in vascular remodeling, a complex cardiopulmonary disease caused by hypoxia. Some research results have shown that ginsenoside Rg1 (Rg1) can improve vascular remodeling, but the effect and mechanism of Rg1 on hypoxia-induced pulmonary hypertension are not clear. The purpose of this study was to discuss the potential mechanism of action of Rg1 on HPH. Methods: C57BL/6 mice, calpain-1 knockout mice and Pulmonary artery smooth muscle cells (PASMCs) were exposed to a low oxygen environment with or without different treatments. The effect of Rg1 and calpain-1 silencing on inflammation, fibrosis, proliferation and the protein expression levels of calpain-1, STAT3 and p-STAT3 were determined at the animal and cellular levels. Results: At the mouse and cellular levels, hypoxia promotes inflammation, fibrosis, and cell proliferation, and the expression of calpain-1 and p-STAT3 is also increased. Ginsenoside Rg1 administration and calpain-1 knockdown, MDL-28170, and HY-13818 treatment showed protective effects on hypoxia-induced inflammation, fibrosis, and cell proliferation, which may be associated with the downregulation of calpain-1 and p-STAT3 expression in mice and cells. In addition, overexpression of calpain 1 increased p-STAT3 expression, accelerating the onset of inflammation, fibrosis and cell proliferation in hypoxic PASMCs. Conclusion: Ginsenoside Rg1 may ameliorate hypoxia-induced pulmonary vascular remodeling by suppressing the calpain-1/STAT3 signaling pathway.

Ephedra has anti-fibrogenic effects by inhibiting the TGF-β/Smad pathway in LX-2 cells (마황(麻黃) 열수 추출물의 TGF-β/Smad 경로 억제를 통한 간섬유화 억제효능)

  • Jea Hyun Yoo;Sang Mi Park;Dae Hwa Jung;Sang Chan Kim
    • Herbal Formula Science
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    • v.32 no.2
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    • pp.141-153
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    • 2024
  • Objective : Ephedrae Herba (Ephedra) has been frequently used in the East Asian traditional medicine including Korea, China and Japan in the clinical treatment of asthma, cold and influenza etc. This study was performed to explore an anti-fibrogenic potential of Ephedra Herba water extract (EHE) using immortalized human hepatic stellate cell line, LX-2 cells. Methods : We examined the anti-fibrogenic effects of EHE on canonical pathway of transforming growth factor-β1 (TGF-β1) signaling in LX-2 cells. Cell viability was measured using the MTT assay. mRNA levels were detected by real-time PCR. Proteins expression were detected by Western blot. Results : Treatment of EHE 30 ㎍/ml did not show any cytotoxicity on LX-2 cells. Pre-treatment of EHE (30 ㎍/mL) significantly inhibited α-smooth muscle actin expression induced by TGF-β1. Additionally, EHE significantly decreased Smad2 and Smad3 phosphorylations, Smad binding element-driven luciferase activity and plasminogen activator inhibitor type 1 expression by TGF-β1. Furthermore, increases of matrix metalloproteinases 2 genes by TGF-β1 was also attenuated by EHE treatment. Conclusion : These results suggest that EHE has an ability to suppress fibrogenic process in activated HSC via inhibition of TGF-β1-TGFBR mediated canonical (Smad dependent) pathway.

Increase in $Na^+-Ca^{2+}$ Exchange Activity in Sarcolemma Isolated from Mesenteric Arteries of Spontaneously Hypertensive Rats

  • Lee, Shin-Woong;Lee, Jeung-Soo;Park, Young-Joo;Park, In-Sook
    • Archives of Pharmacal Research
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    • v.12 no.2
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    • pp.128-134
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    • 1989
  • $Na^+-Ca^{2+}$ exchange process in sarcolemmal vesicles isolated from mesenteric arteries of Wistar-Kyoto normotensive(WKY) and spontaneously hypertensive rats(SHR) was investigated. The sarcolemmal fractions isolated after homogenization and sucrose density gradient centrifugation were enriched with 5'-nucleotidase and ouabain sensitive, $K^+-dependent$ phosphatase activities. When the vesicles were loaded with $Na^+$, a time dependent $Ca^{2+}$ uptake was observed. However, very little $Ca^{2+}$ uptake was observed when the vesicles were loaded with $K^+$, or $Ca^{2+}$ uptake of the $Na^+-loaded$ vesicles was carried out in high sodium medium so that there was no sodium gradient. When the vesicles loaded with $Ca^{2+}$ by $Na^+-Ca^{2+}$ exchange were diluted into potassium medium containing EGTA, $Ca^{2+}$ was rapidly released from the vesicles. $Na^+-dependent\;Ca^{2+}$ uptake was increased in SHR compared to WKY, but passive efflux of preaccumulated $Ca^{2+}$ from the vesicles was decreased in SHR. The data indicate that the membrane vesicles of rat mesenteric arteries exhibit $Na^+-Ca^{2+}$ exchange activity. It is also suggested that changes of this process in vascular smooth muscle cell membrane of SHR may be involved in higher intracellular $Ca^{2+}$ concentration and higher basal tone in SHR.

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Primary leiomyosarcoma of the chest wall in a child : a case report (소아의 흉벽에서 진단된 평활근육종 1례)

  • Choi, Jae Hyuk;Chung, David Chanwook;Lee, Mee Jeong
    • Clinical and Experimental Pediatrics
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    • v.51 no.1
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    • pp.98-101
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    • 2008
  • Leiomyosarcoma is an uncommon soft tissue sarcoma of mesenchymal cell origin, which shows smooth muscle differentiation. Leiomyosarcoma is seldom found in the pediatric population, and accounts for fewer than 2% of all soft tissue sarcomas. Leiomyosarcoma of the chest wall is extremely rare in children. We report here a case of an 8-year-old boy with a primary leiomyosarcoma that was incidentally found as a rib mass. The patient underwent a complete resection for a suspected osteochondroma diagnosed by a three-dimensional chest computed tomography examination. Pathological findings of the mass revealed intersecting fascicles of spindle cells showing cigar-shaped nuclei, inconspicuous nuclear pleomorphism and occasional mitotic figures in the background of a suspected osteochondroma of the rib. This report documents the first description of a leiomyosarcoma possibly arising in an osteochondroma of the rib in a child.

A Case of Lymphangioleiomyomatosis with Pregnancy (임신으로 악화된 폐의 임파관평활근종증 l예)

  • Kim, Seong-Ook;Kim, Min-Gu;Won, Yong-Hwan;Kim, Ho-Cheol;Hwang, Young-Sil;Kim, Jong-Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.3
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    • pp.375-380
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    • 1995
  • The lymphangioleiomyomatosis(LAM) is a rare disorder, which afflicts mainly young woman of childbearing age, characterized by proliferation of immature smooth muscle cell in the lymphatics. We experienced a case of LAM in 26-years-old pregnant woman, confirmed pathologically by inguinal lymph node biopsy. She has suffered from exertonal dyspnea and dry coughing. The symptoms and chest X-ray were aggravated with pregnancy, but improved after delivery with two times of pregnancy. The chest X-ray showed diffuse reticulonodular infiltration and chest HRCT showed diffuse scattered tiny thin-walled cyst of lung parenchyma. We noted chylous ascites of which triglyceride level is 396 mg/dl. After delivery, the symptoms were getting better. We treated with medroxyprogesterone and planned close observation and follow-up.

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Therapeutic implications of microRNAs in pulmonary arterial hypertension

  • Lee, Aram;McLean, Danielle;Choi, Jihea;Kang, Hyesoo;Chang, Woochul;Kim, Jongmin
    • BMB Reports
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    • v.47 no.6
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    • pp.311-317
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    • 2014
  • microRNAs (miRNAs) are a class of small, non-coding RNAs that play critical posttranscriptional regulatory roles typically through targeting of the 3'-untranslated region of messenger RNA (mRNA). Mature miRNAs are known to be involved in global cellular processes, such as differentiation, proliferation, apoptosis, and organogenesis, due to their capacity to target multiple mRNAs. Thus, imbalances in the expression and/or activity of miRNAs are involved in the pathogenesis of numerous diseases, including pulmonary arterial hypertension (PAH). PAH is a progressive disease characterized by vascular remodeling due to excessive proliferation of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). Recently, studies have evaluated the roles of miRNAs involved in the pathogenesis of PAH in these pulmonary vascular cells. This review provides an overview of recent discoveries on the role of miRNAs in the pathogenesis of PAH and discusses the potential for miRNAs as therapeutic targets and biomarkers of PAH.

Combinatorial Physical Stimulation and Synergistically-Enhanced Fibroblast Differentiation for Skin Regeneration (피부 재생능력 촉진을 위한 물리적 복합자극의 활용 연구)

  • Ko, Ung Hyun;Hong, Jungwoo;Shin, Hyunjun;Kim, Cheol Woong;Shin, Jennifer H.
    • Journal of the Korean Society for Precision Engineering
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    • v.32 no.8
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    • pp.755-760
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    • 2015
  • For proper wound healing, dermal contraction and remodeling are critical; during the natural healing process, differentiated fibroblasts called "myofibroblasts" typically undertake these functions. For severe wounds, however, a critical mass of dermal matrix and fibroblasts are lost, making self-regeneration impossible. To overcome this impairment, synthetic wound patches with embedded functional cells can be used to promote healing. In this study, we developed a polydioxanone (PDO)-based cell-embedded sheet on which dermal fibroblasts were cultured and induced for differentiation into myofibroblasts, whereby the following combinatorial physicochemical stimuli were also applied: aligned topology, electric field (EF), and growth factor. The results show that both the aligned topology and EF synergistically enhanced the expression of alpha smooth-muscle actin (${\alpha}$-SMA), a key myofibroblast marker. Our proof-of-concept (POC) experiments demonstrated the potential applicability of a myofibroblast-embedded PDO sheet as a wound patch.