• Archives of Pharmacal Research
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• v.18 no.6
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• pp.376-380
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• 1995

Monocyte adhesion involves specific cell surface receptors, integrins and results in cell differentiation. We have studied expression and regulation of integrin .${\alpha}_5{\beta}_1$ during differntiation of U937 as in vitro model. To determine expression of integrin ${\alpha}_5{\beta}_1$ during differentiation of U937 as in vitro model. To determine expression of integrin ${\alpha}_5{\beta}_1$ genes by RT-PCR (reverse transcription and polymerase chain reaction) method. We determined expression of integrin ${\alpha}_5{\beta}_1$ genes by RT-PCE (reverse transcription and polymerase chain reaction) method. We found that expression of integrin .alpha.5.betha.1 was greatly increased during PMA-induced differentiation of U937 cells and also found that PMA-induced expression of integrin ${\alpha}_5{\beta}_1$ was inhibited by colchicine, microtubule depoly merizing agent. These results indicate that microtubular integrity is associated with expression of integrin. ${\alpha}_5{\beta}_1$ during PMA-induced differentiation of U937 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3891-3895
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• 2013

The purpose of this study was to evaluate the association of expression of ${\alpha}5{\beta}1$-integrin with clinicopathologic features and prognosis in cervical cancer. Levels of ${\alpha}5{\beta}1$-integrin in normal cervical mucosa and cervical cancer tissue were detected with immunohistochemistry. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. ${\alpha}5{\beta}1$-integrin expression was detected in 84.6% (143/169) cervical cancer samples, significantly different from that in normal cervical mucosa (P < 0.05). Positive expression rates of ${\alpha}5{\beta}1$-integrin in patients with poor histologic differentiation, lymph node metastasis, and recurrence were elevated. Using Kaplan-Meier analysis, a comparison of survival curves of low versus high expression of ${\alpha}5{\beta}1$-integrin revealed a highly significant difference in human cervical cancer cases (P < 0.05), suggesting that overexpression of ${\alpha}5{\beta}1$-integrin is associated with a worse prognosis.The ${\alpha}5{\beta}1$-integrin promotes angiogenesis and associates with lymph node metastasis, vascular invasion and poor prognosis of cervical cancer. The current study indicated that ${\alpha}5{\beta}1$-integrin may be an independent prognostic factor for cervical cancer patients.

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.55-66
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• 1998

Pathophysiological mechanism of hemorrhagic fever with renal syndrome (HFRS) is not fully understood. Major clinical findings of HFRS patients are widespread hemorrhage, acute renal failure and shock. Basic lesion is vascular injury with microvascular hemorrhage and relatively little inflammation. According to autopsy findings, renal medulla shows focal hemorrhage, tubular necrosis and interstitial mononuclear infiltrates. The predominant cell type in the renal and pulmonary interstitium is a fibroblast and it participates in the healing process at the injury site by secreting a large amount of extracellular matrix proteins. Cultured human lung fibroblasts and Mongolian gerbil fibroblasts were known to be good host cells for the hantaan virus. It is possible that not only the endothelial cell but also the fibroblast is a target of Hantaan virus and the fibroblast might be involved in the pathogenesis and the healing process in HFRS. Integrins are adhesion molecules, and act as receptors for many extracellular matrix proteins. Recently, there are many reports that cell surface integrins influence on some viral infections or reversely viruses influence on the expression of integrins. The ${\alpha}_5{\beta}_1$ integrin is a major receptor for the fibronectin which is an important extracellular matrix protein secreted by fibroblasts. In this study, the role of ${\alpha}_5{\beta}_1$ integrin in the infection of Hantaan virus was examined by using anti-${\alpha}_5{\beta}_1$, integrin, anti-${\alpha}_5$ integrin and anti-${\beta}_1$, integrin antibodies in chicken embryo fibroblasts (CEF) and Mongolian gerbil fibroblasts(MGF). The treatment of anti-${\alpha}_5{\beta}_1$, integrin antibody in CEF reduced the virion titers 26.8% and the amount of nucleocapsid N protein 32.6% when compared with control CEF. When MGF were treated with anti-${\alpha}_5$, anti-${\beta}_1$ and anti-${\alpha}_5{\beta}_1$ integrin antibodies, virion titers were reduced by 26.5%, 29.4% and 28.7% and the amount of nucleocapsid N protein were reduced by 65.2%, 59.7% and 72.6%. These results suggested that ${\alpha}_5{\beta}_1$ integrin might act as a receptor for the Hantaan virus or blocking of ${\alpha}_5{\beta}_1$ integrin influences on the viral replication in CEF and MGF. It is also possible that the blocking of only one subunit of integrin represents similar results in that of whole molecule.

• Journal of Korean Neurosurgical Society
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• v.57 no.5
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• pp.329-334
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• 2015

Objective : To comparatively investigate the expression of several integrins in specimens of human bone metastases and degenerative bone tissue. Methods : Degenerative cancellous tissue was obtained from a sample of human degenerative spine. Thirteen human specimens were obtained from metastatic spine tumors, whose primary cancer was colon cancer (n=3), hepatocellular cancer (n=3), lung cancer (n=4), and breast cancer (n=3). The expression of vimentin and integrins ${\alpha}v$, ${\beta}1$, and ${\beta}3$ was assessed in metastatic and degenerative specimens by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (qRT-PCR). Results : Immunohistochemical staining showed that vimentin and integrin ${\alpha}v$ was broadly expressed in all tissues examined. By contrast, integrin ${\beta}1$ was weakly expressed only in 38.4% (5/13) of tissues. Integrin ${\beta}3$ was consistently negative in all cases examined. qRT-PCR analysis showed that vimentin gene expression was higher in all metastatic specimens, as compared to degenerative bone. The gene expression of integrin ${\alpha}v$ in breast specimen was significantly higher than others (p=0.045). The gene expression of integrin ${\beta}1$ was also higher in all metastatic specimens than in degenerative bone tissue. The gene expression of integrin ${\beta}3$ was variable. Conclusion : Spinal metastatic tumors have mesenchymal characteristics such as increased expression of vimentin. The increased expression of integrin ${\alpha}v$ and ${\beta}1$ in spine metastatic tumors suggests that adhesive molecules such as integrin may have implications for the prevention of spine metastasis.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.321-328
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• 2017

Steroid sulfatase (STS) is an enzyme responsible for the hydrolysis of aryl and alkyl sulfates. STS plays a pivotal role in the regulation of estrogens and androgens that promote the growth of hormone-dependent tumors, such as those of breast or prostate cancer. However, the molecular function of STS in tumor growth is still not clear. To elucidate the role of STS in cancer cell proliferation, we investigated whether STS is able to regulate the integrin signaling pathway. We found that overexpression of STS in HeLa cells increases the protein and mRNA levels of integrin ${\beta}1$ and fibronectin, a ligand of integrin ${\alpha}5{\beta}1$. Dehydroepiandrosterone (DHEA), one of the main metabolites of STS, also increases mRNA and protein expression of integrin ${\beta}1$ and fibronectin. Further, STS expression and DHEA treatment enhanced phosphorylation of focal adhesion kinase (FAK) at the Tyr 925 residue. Moreover, increased phosphorylation of ERK at Thr 202 and Tyr 204 residues by STS indicates that STS activates the MAPK/ERK pathway. In conclusion, these results suggest that STS expression and DHEA treatment may enhance MAPK/ERK signaling through up-regulation of integrin ${\beta}1$ and activation of FAK.

• BMB Reports
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• v.51 no.5
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• pp.230-235
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• 2018

Bone resorption by multinucleated osteoclasts is a multistep process involving adhesion to the bone matrix, migration to resorption sites, and formation of sealing zones and ruffled borders. Macrophage colony-stimulating factor (M-CSF) and osteopontin (OPN) have been shown to be involved in the bone resorption process by respective activation of integrin ${\alpha}v{\beta}3$ via "inside-out" and "outside-in" signaling. In this study, we investigated the link between signal modulators known to M-CSF- and OPN-induced osteoclast adhesion and spreading. M-CSF- and OPN-induced osteoclast adhesion was achieved via activation of stepwise signals, including integrin ${\alpha}v{\beta}3$, $PLC{\gamma}$, $PKC{\delta}$, and Rac1. Osteoclast spreading induced by M-CSF and OPN was shown to be controlled via sequential activation, consistent with the osteoclast adhesion processes. In contrast to osteoclast adhesion, osteoclast spreading induced by M-CSF and OPN was blocked via activation of $PLC{\gamma}/PKC{\alpha}/RhoA$ signaling. The combined results indicate that osteoclast adhesion and spreading are selectively regulated via $PLC{\gamma}/PKC{\alpha}-PKC{\delta}/RhoA-Rac1$ signaling.

• Molecules and Cells
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• v.40 no.5
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• pp.355-362
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• 2017

The ${\beta}2$ integrins are cell surface transmembrane proteins regulating leukocyte functions, such as adhesion and migration. Two members of ${\beta}2$ integrin, ${\alpha}M{\beta}2$ and ${\alpha}X{\beta}2$, share the leukocyte distribution profile and integrin ${\alpha}X{\beta}2$ is involved in antigen presentation in dendritic cells and transendothelial migration of monocytes and macrophages to atherosclerotic lesions. ${\underline{R}}eceptor$ for ${\underline{a}}dvanced$ ${\underline{g}}lycation$ ${\underline{e}}nd$ ${\underline{p}}roducts$ (RAGE), a member of cell adhesion molecules, plays an important role in chronic inflammation and atherosclerosis. Although RAGE and ${\alpha}X{\beta}2$ play an important role in inflammatory response and the pathogenesis of atherosclerosis, the nature of their interaction and structure involved in the binding remain poorly defined. In this study, using I-domain as a ligand binding motif of ${\alpha}X{\beta}2$, we characterize the binding nature and the interacting moieties of ${\alpha}X$ I-domain and RAGE. Their binding requires divalent cations ($Mg^{2+}$ and $Mn^{2+}$) and shows an affinity on the sub-micro molar level: the dissociation constant of ${\alpha}X$ I-domains binding to RAGE being $0.49{\mu}M$. Furthermore, the ${\alpha}X$ I-domains recognize the V-domain, but not the C1 and C2-domains of RAGE. The acidic amino acid substitutions on the ligand binding site of ${\alpha}X$ I-domain significantly reduce the I-domain binding activity to soluble RAGE and the alanine substitutions of basic amino acids on the flat surface of the V-domain prevent the V-domain binding to ${\alpha}X$ I-domain. In conclusion, the main mechanism of ${\alpha}X$ I-domain binding to RAGE is a charge interaction, in which the acidic moieties of ${\alpha}X$ I-domains, including E244, and D249, recognize the basic residues on the RAGE V-domain encompassing K39, K43, K44, R104, and K107.

• Animal cells and systems
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• v.8 no.1
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• pp.27-32
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• 2004

Endothellial cells are subjected to hemodynamic shear stress, the dragging force generated by blood flow. Shear stress regulates endothelial cell shape, structure, and function, including gene expression. Since endothelial cells must be anchored to their extracellular matrices(ECM) for their survival and growth, we hypothesized that ECMs are crucial for shear-dependent activation of extracellular signalactivated regulated kinase(ERK) that is important for cell proliferation. Shear stress-dependent activation of ERK was observed in cells plated on two different matrices, fibronectin and vitronectin(the two most physiologically relevant ECM in endothelial cells). We then treated bovine aortic endothelial cells(BAECs) with Arg-Gly-Asp(RGD) peptides that block the functional activation of integrin binding to fibronectin and vitronectin, and a nonfunctional peptide as a control. Treatment of cells with the RGD peptides, but not the control peptide, significantly inhibited ERK activity in a concentration-dependent manner. This supports the idea that integrin adhesion to the ligands, fibronectin and vitronectin, mediates shear stress-dependent activation of ERK. Subsequently, whereas antagonists of vitronectin(LM 609, an antibody for integrin ${\alpha}_{\gamma}$/${\beta}_3$ and XT 199, an antagonist specific for integrin ${\alpha}_{\gamma}$/${\beta}_3$) did not have any effect on shear-dependent activation of ERK, antagonists of fibronectin(a neutralizing antibody for integrin ${\alpha}_5$/${\beta}_1$or ${\alpha}_4$${\beta}_1$ and SM256) had an inhibitory effect. These results clearly demonstrate that mechanoactivation of ERK requires anchoring of endothelial cells to fibronectin through integrins.

• Molecules and Cells
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• v.24 no.2
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• pp.240-246
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• 2007

The ${\beta}2$ integrins on leukocytes play important roles in cell adhesion, migration and phagocytosis. One of the ${\beta}2$ integrins, ${\alpha}X{\beta}2$ (CD11c/CD18), is known to bind ligands such as fibrinogen, Thy-1 and iC3b, but its function is not well characterized. To understand its biological roles, we attempted to identify novel ligands. The functional moiety of ${\alpha}X{\beta}2$, the ${\alpha}X$ I-domain, was found to bind plasminogen, the zymogen of plasmin, with moderate affinity ($1.92{\times}10^{-6}M$) in the presence of $Mg^{2+}$ or $Mn^{2+}$. The ${\beta}D-{\alpha}5$ loop of the ${\alpha}X$ I-domain proved to be responsible for binding, and lysine residues ($Lys^{242}$, $Lys^{243}$) in the loop were the most important for recognizing plasminogen. An excess amount of the lysine analog, 6-aminohexanoic acid, inhibited ${\alpha}X$ I-domain binding to plasminogen, indicating that binding is lysine-dependent. The results of this study indicate that leukocytes regulate plasminogen activation, and consequently plasmin activities, through an interaction with ${\alpha}X{\beta}2$ integrin.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.102-102
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• 2002

Heparin-bindin epidermal growth factor (HB-EGF) is one of the EGF family to be expressed at the time of implantation in the mouse uterus. Although HB-EGF has been shown to stimulate the development of embryo and uterus in the mouse, its correlation between cell adhesion molecules remains undefined. Integrin $\alpha$$_{ν}$$\beta$$_3$, one of the cell adhesion molecules, is an important mediator of cell-substratum and cell-cell adhesion in implantation. In the present studies, we investigated the effects of HB-EGF on the embryonic development, initiation of implantation and expression of integrin $\alpha$$_{ν}$$\beta$$_3$ in in vitro culture, blocking of HB-EGF, RT-PCR and immunofluores cence analysis. The results showed that HB-EGF significantly improved the developmental rate of hatched embryos (24.1%, p<0.01) and outgrowth embryos (42.5%, p<0.01). On the other hand, this growth factor showed no offset before the hatching embryonic stage. Analysis of RT-PCR showed that HB-EGF upregulated the expression level of integrina $\alpha$$_{ν}$$\beta$$_3$ subunit genes on the preimplantation embryo and outgrowth of blastocyst (120hr and 144hr after hCG injection). Immunofluorescence analysis showed that the integrin $\alpha$$_{ν}$$\beta$$_3$ subunits localized at the pericellular borders and cell-cell contact areas. Increase in fluorescence intensity was observed in the HB-EGF treated embryos. Intrauterine injection of an anti-HB-EGF antiserum at day 3 significantly decreased the number of implantation sites (14.4, p<0.01) and significantly increased the number of recovered embryos(6.4, p<0.05) at day 5. From these results, it imply that HB-EGF improve the embryo development and accelerated the expression of integrin $\alpha$$_{ν}$$\beta$$_3$ in the preimplantation mouse embryos.