Expression of integrin alphavbeta6 [alphavbeta6] in oral submucous fibrosis: a potentially malignant condition of oral cavity

Oral submucous fibrosis [OSF] is a chronic progressive fibrosing disorder of the oral cavity. A common finding in tissue fibrosis is that stromal fibroblasts become 'activated' myofibroblasts and express a-smooth muscle actin [SMA]. TGF-beta1 is considered to have a central role in inducing this myofibroblastic phenotype, and its expression is increased in numerous fibrotic conditions. The epithelial-specific integrin alphavbeta 6 is not detectable on normal oral keratinocytes but is upregulated during tissue remodelling. alphavbeta 6 is a key activator of TGF-b1 through its interaction with the latency-associated peptide [LAP] of the cytokine. The objective of the study was to investigate the role of alphavbeta 6 integrin in the pathogenesis of OSF. We used immunochemistry to examine expressionn of alphavbeta 6 in 41 cases of OSF compared with 14 cases of fibroepithelial hyperplasia, and found significantly higher expression in OSF [p=0.009]. We carried out a TGF- b1 bioassay using a keratinocyte cell line genetically modified to express high levels of alphavbeta 6 [VB6], and found that inhibition of alphavbeta 6 significantly reduced TGF-b1 activation [p<0.0001]. Co-culture of HFFF2 fibroblasts with VB6 cells induced myofibroblast transdifferentiation, producing a marked increase in SMA expression. This was inhibited using anti- alphavbeta 6 antibodies, confirming that myofbroblast generation was alphavbeta 6-dependent. In conclusion, these data show that alphavbeta 6-dependent TGF-b1 activation promotes myofibroblast transdifferentiation, and may be responsible, in part, for the chronic fibrosis seen in OSF

Pinopodes

Pinopodes are balloon-like projections that arise from the endometrial surface in mice, rats and humans during the window of receptivity and are best viewed using scanning electron microscopy. Differences are seen in the shape, size and content of pinopodes between rodents and humans. The diameter of pinopodes in rats is 3.0-4.0 microm and in mice and humans it is 6 microm. The percentage of luminal epithelium covered by pinopodes during the window of receptivity varies in rats from 5.5 to 20%, in mice from 0.6 to 20% and in humans from 0 to 12%. The formation of pinopodes in both the rodent and human endometrium appears to be progesterone dependent, whereas administration of estradiol results in their rapid loss. Although the biological function of pinopodes is less well understood, a correlation between the number of pinopodes and implantation rate has been revealed. During implantation, pinopodes interdigitate with microvilli on the syncytiotrophoblast surface of blastocysts. Very few markers have revealed the presence of pinopodes; these include integrins, leukaemia inhibitory factor, heparin-binding epidermal-like growth factor, glutaredoxin, Hoxa-10 and Mucin 1. Clinically, pinopodes are the best studied endometrial factors involved in implantation. In conclusion, pinopodes are a good marker for endometrial receptivity. Further studies other than endometrial biopsy are needed to demonstrate the presence of pinopodes for timing of endometrial receptivity to increase the pregnancy rate in programmes on in-vitro fertilization

Moléculas de cooperación y regulación durante la migración celular en la respuesta inflamatoria / Molecules for cooperation and regulation during cell migration in the inflammatory response

En la superficie de todas las células existen estructuras sacarídicas, dentro de sus múltiples funciones fisiológicas se ha logrado identificar que funcionan como comunicadores intercelulares. En el caso de los leucocitos estas estructuras le permiten, por mecanismos de adherencia, identificar a los sitios de inflamación, este proceso se efectúa gracias a la interacción específica de diversas familias de glicoproteínas de superficie celular entre las que se considera a las denominadas "selectinas", las integrinas y las moléculas pertenecientes a la superfamilia de las inmunoglobulinas. En este Trabajo, se revisan las características moleculares de estas proteínas adhesivas y, los diversos procesos inflamatorios en los que están involucradas