• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.225-230
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• 2008

Netrins are secreted molecules and involved in axon guidance, cell migration and tumor development. Recent studies revealed that netrins perform novel functions in such processes as epithelial development and angiogenesis without operating through the classical netrin receptors, DCC (Deleted in Colorectal Cancer) and Unc5h. In the present study, we investigated the roles of netrin-1 and its receptors in cell spreading of human glioblastoma cells, and found that netrin-1 haptotactically enhanced fibronectin-induced cell spreading and focal adhesion formation in U373 glioblastoma cells. Netrin-1 binding to the U373 cell membrane was blocked by an antibody against ${\alpha}v$ integrin subunit, but not by an anti-DCC or anti-Unc5h antibody. In addition, enhancement of the fibronectin response by netrin-1 was abrogated by a function blocking antibody against integrin ${\alpha}v{\beta}3$. Since the ${\alpha}v$ subunit of the integrin family plays an important role in the pathophysiological aspects of cell migration, including tumor angiogenesis and metastasis, our data provide important insight into the molecular mechanism of netrin function.

• 대한유전성대사질환학회지
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• 제5권1호
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• pp.126-132
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• 2005

Glanzmann's thrombasthenia는 혈소판 표면의 fibrinogen과 von Willebrand factor(vWF)의 수용체인 당단백 ${\alpha}_{IIb}{\beta}_3$의 결함으로 인해 ristocetin을 제외한 모든 agonist들에 대해 응집 이상을 보여 혈소판 수와 형태는 정상이면서 심한 출혈 시간의 연장을 가져오는 상염색체 열성 유전 질환이다. 저자들은 II형 Glanzmann's thrombasthenia로 진단된 4세 여아에서 ${\beta}_3$ 유전자의 이상 중 보고되지 않은 부위의 이상을 최초로 밝혔기에 문헌 고찰과 함께 보고하는 바이다.

• 해부∙생물인류학
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• 제31권4호
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• pp.143-149
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• 2018

접촉피부염은 피부가 이물질과 접촉함으로써 일어나는 염증반응으로 백혈구 혈관외유출이 매우 중요한 역할을 한다는 것은 잘 알려진 사실이다. 선행연구 결과 CD99가 ${\beta}1$ 인테그린 의존적 메커니즘을 통하여 단핵구의 혈관외유출을 조절하며, 따라서 염증 질환에 대한 치료제 개발의 신규 표적 분자일 가능성이 제시되었다. 본 연구에서는 CD99 유래 펩타이드인 CD99CRIII3가 단핵구의 혈관외유출과 접촉피부염 생쥐 모델에서 염증 반응을 억제하는지를 조사하였다. 인간 단핵구 세포주인 U937를 CD99CRIII로 처리할 경우 농도의존적으로 ${\beta}1$ integrin의 활성도가 감소되었으며, 이 세포주의 사람제대정맥내피세포에의 부착과 혈관외유출도 억제되었다. 나아가 CD99CRIII3는 포르볼 미리스테이트 아세테이트 처리에 의해 유발된 생쥐 접촉피부염 모델에서 Evans Blue의 혈관투과와 귀조직 무게를 농도 의존적으로 억제하였다. 이러한 결과들은 CD99CRIII3가 단핵구의 혈관외유출과 접촉피부염 동물 모델에서 일어나는 염증반응을 억제함을 보여준다. 이와 같이, 본 연구는 CD99 유래 펩타이드가 피부 염증질환에 대한 치료제로 개발될 가능성이 있음을 제시한다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.231.3-232
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• 2003

The biomedical applications of chitosan have been widely researched. FN mediates its biological effects through binding to the hetero-dimeric transmembrane glycoproteins, integrins, which physically couple the cytoskeleton to the ECM. FN binds to the integrin through a consensus site including the Arg-Gly-Asp (RGD) sequence within tenth type III module (Ruoslahti & Pierschbacher 1987). A short sequence Pro-His-Ser-Arg-Asn (PHSRN) has also been identified as a synergistic motif within ninth type III module for binding to ${\alpha}$5${\beta}$1 integrin (Aota et al. 1994). (omitted)

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.80-88
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• 2002

Recent studies demonstrate that collagen IV selectively pro-motes the repair of physiological processes in sublethally injured renal proximal tubular ceils (RPTC). We sought to further define the mechanisms of cell repair by measuring the effects of toxicant injury and stimulation of repair by L-ascorbic acid-2-phosphate (AscP), exogenous collagen IV, or function-stimulating integrin antibodies on the expression and subcellular localization of collagen-binding integrins (CBI) in RPTC. Expression of CBI subunits ${\alpha}_1$, ${\alpha}_2$, and ${\beta}_1$ in RPTC was not altered on day 1 after sublethal injury by S-(1,2-dichlorovinyl)-L-cysteine (DCVC). On day 6, expression of ${\alpha}_1$ and ${\beta}_1$ subunits remained unchanged, whereas a 2.2-fold increase in ${\alpha}_2$ expression was evident in injured RPTC. CBI localization in control RPTC was limited exclusively to the basal membrane. On day 1 after injury, RPTC exhibited a marked inhibition of active $Na^+$ transport and a loss of cell polarity characterized by a decrease in basal CBI localization and the appearance of CBI on the apical membrane. On day 6 after injury, RPTC still exhibited marked inhibition of active $Na^+$ transport and localization of CBI to the apical membrane. However, DCVC-injured RPTC cultured in pharmacological concentrations of AscP (500 ${\mu}$M)or exogenous collagen IV (50 ${\mu}$g/ml) exhibited an increase inactive $Na^+$ transport, relocalization of CBI to the basal membrane, and the disappearance of CBI from the apical membrane on day 6. Function-stimulating antibodies to CBI ${\beta}_1$ did not promote basal relocalization of CBI despite stimulating the repair of $Na^+$/$K^+$-ATPase activity on day 6 after injury. These data demonstrate that DCVC disrupts integrin localization and that physiological repair stimulated by AscP or collagen IV is associated with the basal relocalization of CBI in DCVC-injured RPTC. These data also suggest that CBI-mediated repair of physiological functions may occur independently of integrin relocalization.

• 대한두경부종양학회지
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• 제14권2호
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• pp.236-243
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• 1998

1991년부터 1997년월까지 7년간 한림대학교 이비인후과학교실에서 국소침범한 갑상선암으로 치료를 받은 10명의 환자들을 후향적으로 검토하여 다음과 같은 결과를 얻었다. 1) 성별 분포는 남녀비는 1:2.3이었으며 연령별 분포는 60대 이상이 7명으로 노인에 호발함을 알 수 있었다. 2) 임상승상은 애성이 5례(50%)로 가장 많았으며 무증상이면서 경부종괴로 온 경우가 3례 그외에 연하곤란, 호흡곤란 객혈 등이었다. 3) 침범된 구조는 기관 7례, 반회후두신경과 종격동임파절이 각각 5례, 경부식도 3례, 경동맥 3례, 기관주위임파절 3례, 하인두 1례, 미주신경 1례 순이었다. 4) 침범된 구조물들에 대한 수술로는 기관 수상절제술 및 단단문합술이 1례. 기관 수상절제와 윤상기관성형술 1례, 기관 창절제술 및 일차봉합술 1례. 기관 창절제술 및 흉쇄유돌근-근막피판재건술 1례, 기관 면도식절제술 1례, 식도 부분절제술 2례, 식도 면도식절제술 1례, 편측 윤상후두절제술 1례, 윤상연골 부분절제술 및 흉쇄유돌근-근골막피판재건술 1례, 갑상연골 면도식절제술 1례, 반회후두신경절제술이 2례, 미주신경절제술 1례, 경동맥절제술 및 $Gortex^{\circledR}$를 이용한 재건술 2례, 경동맥 면도식절제술 1례 등이었다. 이상에서 국소침범한 갑상선암은 대부분의 경우 가능한 완전절제를 시도하였으나 광범위 절제 후 재건술의 어려움이 있었으며 또한 대부분이 노인 환자로서 전신상태에 따른 예후가 불량한 경우가 있었다. 따라서 각 환자의 나이와 침범 정도에 따른 개별적인 술식으로 치료방법을 선택하는 것이 중요할 것으로 사료된다.하다고 생각된다. 6) 횡문근육종과 골육종의 경우 3례중 2례에서 광범위한 수술적 제거후 방사선치료를 병행하였으며, 현재 무병생존 중이고, 1례는 화학요법과 방사선치료의 병합요법을 시행하였으나 실패하였다. 육종의 경우 광범위한 수술적 절제가 가장 좋은 치료로 사료되며, 미세잔존암이 남아있는 경우는 방사선 치료의 병합이 필요하리라 생각된다.\beta$4-tyrosine phosphorylation site (Clone M)을 얻었다. 암 세포의 부착 및 침투 능력의 기능적 연구로 모노 클로날 항체와 fibronectin, laminin, Matrigel을 단백질 기질로 사용하였으며 결과 비교를 위하여 pRc/CMV 벡터만 주입시켰던 클로운과 방광암 세포주를 $\beta$4 integrin 음성 대조군으로 또한 이 Integrin의 높은 발현을 보이는 두경부 편평상피암 세포주를 양성 대조군으로 이용하였다. 결과 : 세포부착능력에 있어서 온전한 $\beta$4 cytoplasmic domain이 존재하는 클로운이 laminin에 강한 부착능력을 보였으나 fibronectin의 부착정도는 $\beta$4 integrin의 표현정도와 관계없이 모든 클로운에서 비슷하였다. Matrigel을 투과하는 암세포 침윤 능력에서는 $\beta$4 integrin의 표현이 존재하는 클로운들이 투과 능력이 높았으나 세포외 리간드가 없는 control membrane을 사용하였을 때와 비교하여 투과능력의 차이를 보이지 않았다. 결론 : 유전자 주입(transfection) 방법으로

• Annals of dermatology
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• 제30권6호
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• pp.694-700
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• 2018

Background: Kaempferol (3,4',5,7-tetrahydroxyflavone) is a flavonoid known to have a wide range of pharmacological activities. The 3-OH group in flavonoids has been reported to determine antioxidant activities. Objective: We tested whether kaempferol can affect the expression of integrins and the stem cell fate of interfollicular epidermal stem cells. Methods: Skin equivalent (SE) models were constructed, and the expression levels of stem cell markers and basement membrane-related antigens were tested. The immunohistochemical staining patterns of integrins, p63, and proliferating cell nuclear antigen (PCNA) were compared between kaempferol- and apigenin-treated SE models. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of integrins. Results: Kaempferol increased the thickness of the epidermis when added to prepare SEs. In addition, the basal cells of kaempferol-treated SEs appeared more columnar. In the immunohistological study, the expression of integrins ${\alpha}6$ and ${\beta}1$ and the numbers of p63- and PCNA-positive cells were markedly higher in the kaempferol-treated model. However, apigenin showed no effects on the formation of three-dimensional skin models. RT-PCR analysis also confirmed that kaempferol increased the expression of integrin ${\alpha}6$ and integrin ${\beta}1$. Conclusion: Our findings indicated that kaempferol can increase the proliferative potential of basal epidermal cells by modulating the basement membrane. In other words, kaempferol can affect the fate of interfollicular epidermal stem cells by increasing the expression of both integrins ${\alpha}6$ and ${\beta}1$. These effects, in particular, might be ascribed to the 3-OH group of kaempferol.

• Molecules and Cells
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• 제40권2호
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• pp.109-116
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• 2017

Soybean agglutinin (SBA) is an anti-nutritional factor of soybean, affecting cell proliferation and inducing cytotoxicity. Integrins are transmembrane receptors, mediating a variety of cell biological processes. This research aims to study the effects of SBA on cell proliferation and cell cycle progression of the intestinal epithelial cell line from piglets (IPEC-J2), to identify the integrin subunits especially expressed in IPEC-J2s, and to analyze the functions of these integrins on IPEC-J2 cell cycle progression and SBA-induced IPEC-J2 cell cycle alteration. The results showed that SBA lowered cell proliferation rate as the cell cycle progression from G0/G1 to S phase (P < 0.05) was inhibited. Moreover, SBA lowered mRNA expression of cell cycle-related gene CDK4, Cyclin E and Cyclin D1 (P < 0.05). We successfully identified integrins ${\alpha}2$, ${\alpha}3$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ in IPEC-J2s. These five subunits were crucial to maintain normal cell proliferation and cell cycle progression in IPEC-J2s. Restrain of either these five subunits by their inhibitors, lowered cell proliferation rate, and arrested the cells at G0/G1 phase of cell cycle (P < 0.05). Further analysis indicated that integrin ${\alpha}2$, ${\alpha}6$, and ${\beta}1$ were involved in the blocking of G0/G1 phase induced by SBA. In conclusion, these results suggested that SBA lowered the IPEC-J2 cell proliferation rate through the perturbation of cell cycle progression. Furthermore, integrins were important for IPEC-J2 cell cycle progression, and they were involved in the process of SBA-induced cell cycle progression alteration, which provide a basis for further revealing SBA anti-proliferation and anti-nutritional mechanism.

• 대한한방종양학회지
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• 제4권1호
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• pp.177-197
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• 1998

This experimental study was carried out to evaluate the effect of Yipahnsan on angiogenic inhibition mechanism. This study investigates the effects of Yipahnsan on angiogenic inhibition mechanism evaluate cell adhesive inhibition effect, DNA fragmantaion analysis, nuclear condensation assay, FACScan analysis, angiogenic lumen formation assay, immunocytochemistry analysis, RT-PCR for mRNA expression, western blot analysis, confocal analysis for $Ca^{2+}influx$. The results were summarized as follows : 1. The cell adhesive inhibition ability was strongly increased from $5{\mu}g/ml$ on ECV304 cell line and ECVPAR cell line. 2. YY water extract caused $G_0/G_1$ arrest peak to existed on the ECV304 cell line. 3. YY water extract caused inhibition of proliferation and inducement of apoptosis on the collagen coated plate in ECV304 cell line. 4. YY water extract inhibited the lumen formation on the matrigel coated plate in ECV304 cell line. 5. YY water extract inhibited the expressions of LFA-1 and ELAM-1 on ECV304 cell line and ECVPAR cell line. 6. YY water extract inhibited the expressions of MMP-9 and uPA on ECV304 cell line and ECVPAR cell line. 7. YY water extract inhibited the expression of integrin ${\alpha}_v{\beta}_3$ on ECV304 cell line and ECVPAR cell line. 8. YY water extract decreased the change of $Ca^{2+}$ in intracellular on ECV304 cell line and ECVPAR cell line. According to the results, Yipahnsan showed to be a key antagonist of integrin ${\alpha}_v{\beta}_3$, and to be induction of apoptosis by p53 through flow cytometry. This report also demonstrated that expressions of MMP-9 and uPA were blocked under the angiogenesis model. Thus, we suggested that Yipahnsan blocks angiogenesis by inducing apoptosis in ECV304 and ECVPAR cell lines, and another oriental herbal medicine that treats qi-stagnation and blood-stasis type also has angiogenic inhibition effects.

• 대한한방종양학회지
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• 제4권1호
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• pp.17-36
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• 1998

This experimental study was carried out to evaluate the effects of Hwallakhyoreungdan on angiogenic inhibition mechanism. In order to investigate the effects of Hwallakhyoreungdan on angiogenic inhibition mechanism, MTT assay, cell adhesive inhibition effect, DNA fragmantaion analysis, Nuclear condensation assay, FACScan analysis, Angiogenic lumen formation assay, Immunocytochemistry analysis, RT-PCR for mRNA expression, Western blot analysis and Confocal analysis for $Ca^{2+}$ change were performed. The results were summarized as follows: 1. The cell adhesive inhibition ability was strong from $5{\mu}g/ml$. 2. The $G_0/G_1$ arrest peak was existed on ECV304 cell-line. 3. The cells on Collagen plate were inhibition of proliferation and inducement of apoptosis by HR water extract. 4. Angiogenic lumen formation was inhibited by HR water extract. 5. LFA-1 and ELAM-1's expression were inhibited by HR water extract. They are commenly participation on inflammation and tumor regeneration. 6. The expression of MMP-9 and uPA were inhibited by HR water extract. 7. The expression of integrin ${\alpha}_v{\beta}_3$ was inhibited by HR water extract. 8. The expression of intracellular molecule were successively inhibited by HR water extract therefore the proliferation of ECV304 cell line was stopped and apoptosis was induced. 9. The change of $Ca^{2+}$ was decreased by HR water extract it cause confusion of signal transduction pathway therefore it was take part in apoptosis. According to the results, Hwallakhyoreungdan showed to be a key antaonist of integrin ${\alpha}_v{\beta}_3$, and to be induction of apoptosis by p53 through flow cytometry. This report also demonstrated that expressions of MMP-9 and uPA was blocked under the angiogenesis model. Thus, we suggests that Hwallakhyoreungdan blocks angiogenesis by inducing apoptosis of ECV304 and ECVPAR cell lines and another oriental herbal medicine that treats blood-stasis type also has angiogenic inhibition effects.