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1.
J Invest Dermatol ; 133(2): 386-93, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22951719

RESUMEN

The most distinctive feature of keloid is the extreme deposition of extracellular matrix, including collagens and proteoglycans (PGs). The focus of this study was the PG versican, which presumably defines keloid volume because of its ability to retain large amounts of water through its component glycosaminoglycans (GAGs). The excessive deposition of versican in keloids was examined by immunohistochemical analysis and by upregulation of the versican gene in these lesions by real-time PCR. The latter showed that mesenchymal cells derived from keloid lesion (KL) cells continue to exhibit above-normal versican production in culture. To establish a model of GAG deposition in keloids, collagen sponges seeded with KL cells (KL-SPos) were implanted in the subcutaneous space of nude mice. After 1 month, the KL-SPos were significantly heavier than the fibroblast (Fb)-seeded sponges (Fb-SPos). This ex vivo model was subsequently used to examine an inhibitory ability of IL-1ß that was identified to reduce versican in vitro. IL-1ß or chondroitinase ABC, when injected directly, successfully reduced the weight of the KL-SPos. Thus, on the basis of the change in weight of the seeded sponges, this ex vivo model can be used to test therapies aimed at reducing or inhibiting keloid formation and to study the pathogenesis of this aberrant response.


Asunto(s)
Queloide , Versicanos/genética , Versicanos/metabolismo , Adulto , Animales , Condroitina ABC Liasa/farmacología , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Femenino , Fibroblastos/citología , Fibroblastos/trasplante , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Glicosaminoglicanos/genética , Glicosaminoglicanos/metabolismo , Humanos , Interleucina-1beta/farmacología , Queloide/metabolismo , Queloide/patología , Queloide/terapia , Masculino , Ratones , Ratones Desnudos , Cultivo Primario de Células , Tapones Quirúrgicos de Gaza , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiología
4.
Genes Cells ; 12(6): 787-96, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17573778

RESUMEN

T-cadherin is a glycosyl-phosphatidylinositol (GPI) anchored cadherin molecule. We previously reported that T-cadherin is normally expressed on the basal keratinocytes of the epidermis and is down-regulated in cutaneous squamous cell carcinoma (SCC). We found that expression of T-cadherin in cutaneous squamous carcinoma cells regulated level of surface beta1 integrin, which functioned as extracellular matrix (ECM) receptor. Involvement of T-cadherin in beta1 integrin trafficking was studied using three different stable cell lines with cytomegalovirus (CMV)-driven over-expression, tetracycline (Tet)-inducible expression and RNAi-mediated suppressed expression of T-cadherin. Pulse-chase analysis using a cholesterol-depleting reagent and a tyrosine kinase inhibitor showed that beta1 integrin mainly internalized via caveolae. Over-expression of T-cadherin suppressed the internalization of both beta1 integrin and cholera toxin (CTX), a marker of caveolae-mediated endocytosis. By Western blot analysis of tyrosine-kinase target molecules, we demonstrated a reduced level of EGF receptor (EGFR)-phosphorylation in T-cadherin over-expressing cells. In addition, studies using EGF and EGFR specific inhibitors revealed that EGFR activation stimulated beta1 integrin internalization. Taking these results together, T-cadherin may modulate cell-matrix adhesion in basal keratinocytes as well as invasive potency in SCC by regulating surface level of beta1 integrin.


Asunto(s)
Cadherinas/biosíntesis , Carcinoma de Células Escamosas/metabolismo , Regulación Neoplásica de la Expresión Génica , Regulación de la Expresión Génica , Integrina beta1/metabolismo , Neoplasias Cutáneas/metabolismo , Cadherinas/metabolismo , Adhesión Celular , Línea Celular , Receptores ErbB/metabolismo , Matriz Extracelular/metabolismo , Glicosilfosfatidilinositoles/química , Humanos , Queratinocitos/metabolismo , Interferencia de ARN , Transducción de Señal
5.
J Biol Chem ; 278(20): 18538-43, 2003 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-12626509

RESUMEN

Septins are a family of conserved proteins implicated in a variety of cellular functions such as cytokinesis and vesicle trafficking, but their properties and modes of action are largely unknown. Here we now report findings of immunocytochemical and biochemical characterization of a mammalian septin, MSF-A. Using an antibody specific for MSF subfamily proteins, MSF-A was found to be expressed predominantly in mammary human mammary epithelial cells (HMEC). MSF-A was associated with microtubules in interphase HMEC cells as it localized with the mitotic spindle and the bundle of microtubule at midzone during mitosis. Biochemical analysis revealed direct binding of MSF-A with polymerized tubulin through its central region containing guanine nucleotide-interactive motifs. GTPase activity, however, was not required for the association. Conditions that disrupt the microtubule network also disrupted the MSF-A-containing filament structure, resulting in a punctate cytoplasmic pattern. Depletion of MSF-A using small interfering RNAs caused incomplete cell division and resulted in the accumulation of binucleated cells. Unlike Nedd5, an MSF mutant deficient in GTPase activity forms filament indistinguishable from that of the wild type in COS cells. These results strongly suggest that septin filaments may interact not only with actin filaments but also with microtubule networks and that GTPase activity of MSF-A is not indispensable to incorporation of MSF-A into septin filaments.


Asunto(s)
Mama/metabolismo , Proteínas del Citoesqueleto/química , Células Epiteliales/metabolismo , Proteínas de Unión al GTP/química , Secuencias de Aminoácidos , Animales , Células COS , Línea Celular , Células Cultivadas , Citocalasina B/farmacología , Citoplasma/metabolismo , Proteínas del Citoesqueleto/metabolismo , Demecolcina/farmacología , GTP Fosfohidrolasas/metabolismo , Proteínas de Unión al GTP/metabolismo , Células HeLa , Humanos , Microscopía Fluorescente , Microtúbulos/metabolismo , Mitosis , Mutación , Plásmidos/metabolismo , Unión Proteica , Interferencia de ARN , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección , Tubulina (Proteína)/química
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