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Results for “Integrin alpha2beta1”

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At least 325 records · Page 18Linked to original sources
PubMed1999

Alpha 2 beta 1 integrin mediates dermal fibroblast attachment to type VII collagen via a 158-amino-acid segment of the NC1 domain.

Dermal fibroblasts are in apposition to type VII (anchoring fibril) collagen in both unwounded and wounded skin. The NC1 domain of type VII collagen contains multiple submodules with homology to known adhesive molecules, including fibronectin type III-like repeats and a potential RGD cell attachment site. We previously reported the structure and matrix binding properties of authentic and recombinant NC1. In this study, we examined the interaction between dermal fibroblasts and the NC1 domain of type VII collagen. We found that both recombinant and authentic NC1 vigorously promoted human fibroblast attachment. Adhesion of fibroblasts to NC1 was dose dependent, saturable, and abolished by both polyclonal and monoclonal antibodies to NC1. Cell adhesion to NC1 was divalent cation dependent and specifically inhibited by a monoclonal antibody directed against the alpha2 or beta1 integrin subunits, but not by the presence of RGD peptides. Furthermore, the cell-binding activity of NC1 was not conformation dependent, since heat-denatured NC1 still promoted cell adhesion. Using a series of recombinant NC1 deletion mutant proteins, the cell binding site of NC1 was mapped to a 158-aa (residues 202-360) subdomain. We conclude that human dermal fibroblasts interact with the NC1 domain of type VII collagen and this cell-matrix interaction is mediated by the alpha2beta1 integrin and is RGD independent.

Binding Sites↗
PubMed2006

Effect of homocysteine on platelet activation induced by collagen.

OBJECTIVE: The present study investigated the effects of homocysteine on platelet activation induced by collagen and the downstream signaling pathways potentially involved in these effects. METHODS: Washed human platelets were incubated with homocysteine and collagen type I. The effects of homocysteine on platelet aggregation and adhesion and the tyrosine phosphorylation of total platelet proteins, Src kinase, and phospholipase-Cgamma2 (PLCgamma2) were studied. RESULTS: Homocysteine (10 to 100 microM) increased collagen-induced aggregation of washed platelets. Upon homocysteine (50 to 100 microM) treatment, platelet deposition to collagen-coated surface was significantly augmented under the low shear rate model (100/s) but not under the high shear rate model (1600/s). Collagen-stimulated total protein tyrosine phosphorylation in platelets was further enhanced by incubation with homocysteine. This effect was almost abrogated by genistein. Homocysteine potentiated collagen-stimulated tyrosine phosphorylation of the Src kinase and PLCgamma2, which was partly decreased by integrin beta1 blocking antibody. CONCLUSION: Homocysteine (at 10 to 100 microM) potentiates collagen type I induced-platelet activation through signaling components of glycoprotein VI and integrin alpha2beta1 pathway. Our results suggested that upregulation of tyrosine phosphorylation of proteins such as Src and PLCgamma2 is involved in the downstream signaling events of homocysteine stimulation in human platelets.

Blotting, Western↗
PubMed2004

Integrin engagement differentially modulates epithelial cell motility by RhoA/ROCK and PAK1.

Integrin-ligand binding regulates tumor cell motility and invasion. Cell migration also involves the Rho GTPases that control the interplay between adhesion receptors and the cytoskeleton. We evaluated how specific extracellular matrix ligands modulate Rho GTPases and control motility of human squamous cell carcinoma cells. On laminin-5 substrates, the epithelial cells rapidly spread and migrated, but on type I collagen the cells spread slowly and showed reduced motility. We found that RhoA activity was suppressed in cells attached to laminin-5 through the alpha3 integrin receptor. In contrast, RhoA was strongly activated in cells bound to type I collagen and this was mediated by the alpha2 integrin. Inhibiting the RhoA pathway by expression of a dominant-negative RhoA mutant or by directly inhibiting ROCK, reduced focal adhesion formation and enhanced cell migration on type I collagen. Cdc42 and Rac and their downstream target PAK1 were activated following adhesion to laminin-5. PAK1 activation induced by laminin-5 was suppressed by expression of a dominant-negative Cdc42. Moreover, constitutively active PAK1 stimulated migration on collagen I substrates. Our results indicate that in squamous epithelial cells, collagen-alpha2beta1 integrin binding activates RhoA, slowing cell locomotion, whereas laminin-5-alpha3beta1 integrin interaction inhibits RhoA and activates PAK1, stimulating cell migration. The data demonstrate that specific ligand-integrin pairs regulate cell motility differentially by selectively modulating activities of Rho GTPases and their effectors.

Adenoviridae↗
PubMed1998

Nucleotide polymorphisms in the alpha2 gene define multiple alleles that are associated with differences in platelet alpha2 beta1 density.

Three allelic differences in the alpha2 gene are associated with expression levels of the alpha2beta1 integrin on the platelet surface. We have previously defined two linked silent polymorphisms in the alpha2 gene coding region at nucleotides 807 (C or T) and 873 (G or A). We have now identified one rarer nucleotide polymorphism in the coding region at nucleotide 837 (T or C) and four additional linked polymorphisms within the introns that flank these coding sequences. Moreover, we have determined that the alloantigenic Br polymorphism, which resides in a distal coding region at nucleotide 1648, is also linked to the 837 polymorphism. Thus, three alpha2 gene alleles, defined by eight nucleotide polymorphisms, have now been discovered. Allele 1 (807T/837T/873A/Brb) is associated with increased levels of alpha2beta1; allele 2 (807C/837T/873G/Brb) and allele 3 (807C/837C/873G/Bra) are each associated with lower levels of alpha2beta1. Finally, we also show here that the rate of platelet attachment to type I collagen in whole blood under conditions of high shear rate (1,500/s) is proportional to the density of alpha2beta1 receptors on the platelet surface. Thus, the density of platelet alpha2beta1 could have an important impact on platelet adhesion to collagen in whole blood and therefore on platelet function in vivo, contributing to an increased risk of thrombosis or to bleeding in relevant disease states.

Alleles↗
PubMed1999

Review article: platelet-collagen interactions: membrane receptors and intracellular signalling pathways.

Platelet adhesion to and activation by exposed subendothelial collagen plays a critical role in normal haemostasis and pathological thrombosis. Recent advances in elucidating the mechanisms underlying platelet-collagen interaction support a 'two-site, two-step' model. Direct platelet binding to integrin alpha2beta1 mainly sustains adhesion and allows recognition of glycoprotein VI. The latter interaction is responsible for characteristic intracellular signalling events leading to p72Syk and PLCgamma2 activation. The present review describes the known collagen receptors on platelets and discusses the current understanding of signal transduction promoted by collagen.

Blood Platelets↗
PubMed1998

Can alterations in integrin and laminin-5 expression be used as markers of malignancy?

Development of squamous cell carcinomas (SCCs) involves alterations in the adhesive interactions in the epithelium and invasion through the basement membrane. Therefore, changes in the expression of receptors and ligands involved in cell-cell and cell-matrix adhesion may be essential for the transformation of a premalignant into a malignant lesion. The aim of this study was to examine if expression of specific cell adhesion molecules can be used as markers of malignant development. By immunohistochemistry, we examined the expression pattern of integrins alpha2beta1, alpha3beta1, alpha6beta4 and laminin-5 in biopsies from SCCs (n=18), premalignant lesions (leukoplakias, n=21) and non-premalignant tissue with chronic inflammation (n=11). In poorly differentiated SCCs, patchy loss of alpha3beta1, alpha6beta4 and laminin-5 expression was pronounced at the invasion front, whereas there was a tendency to increased expression of alpha2beta1. Analogous to the SCCs, biopsies from the leukoplakias and the non-premalignant inflammatory tissue showed alterations of the expression of alpha3beta1 and alpha6beta4 in the basal cell layers and of laminin-5. However, a characteristic finding in biopsies from leukoplakias was loss of alpha2beta1 and alpha3beta1 in the suprabasal cells. There was no unequivocal expression of the adhesion molecules distinguishing between inflammatory tissue, premalignant, and malignant lesions.

Adult↗
PubMed2000

Integrins as mediators of epithelial cell-matrix interactions in the human small intestinal mucosa.

The intestinal epithelium is a highly dynamic tissue, which depends on a variety of factors for the regulation of its rapid renewal and expression of digestive functions. Over the last 10 years, it has become evident that among these factors are cell interactions with the extracellular matrix, more specifically with the underlying basement membrane, through a series of specific cell membrane receptors, many of which are integrins. Integrins regulate the assembly of adhesive junctions as well as the activation of various signaling pathways, leading to the modulation of gene expression. The analysis of the integrin repertoire along the crypt-villus axis in the human small intestinal epithelium identifies a number of beta1 and beta4 integrins, showing differential patterns of expression relative to its two functional compartments. Among them are the integrins alpha3beta1, alpha7Bbeta1 and the functional form of alpha6beta4 that appear to be related, in concert with the distribution of their ligands, to the process of intestinal cell differentiation, and the integrins alpha2beta1, alpha1beta1, alpha5beta1, and the non-functional form of alpha6beta4 that seem to be coupled with the undifferentiated/proliferative status of crypt cells. These observations delineate the potential complexity of the organization of epithelial cell-matrix interactions involved in the maintenance of the human intestinal crypt-villus axis.

Basement Membrane↗
PubMed1997

Expression of cell adhesion molecules in normal nerves, chronic axonal neuropathies and Schwann cell tumors.

Cell adhesion molecules (CAMs) play a role in the normal development and regeneration of tissues as well as in the biological behaviour of tumors. We studied the immunohistochemical expression of various CAMs, such as neural cell adhesion molecule (NCAM), its polysialylated isoform (PSA-NCAM), epithelial (E-) cadherin, and beta1 integrins (alpha2beta1, alpha5beta1, alpha6beta1) in a series of frozen specimens of 10 normal nerves, 5 axonal neuropathies, 26 benign Schwannomas and 2 malignant peripheral nerve sheath tumors (MNST). NCAM was expressed by non-myelinating Schwann cells from normal nerves and overexpressed by Schwann cells from patients with chronic axonal neuropathies and Schwannomas. The expression was lower in MNST. Expression of PSA-NCAM was heterogeneously displayed by Schwann cells from the various tissues studied. Anti E-cadherin immunoreactivity was present in myelin sheath in normal nerves and axonopathies. It was expressed in some Schwannomas especially in vestibular Schwannomas. Integrins VLA alpha2 and VLA alpha6 were widely expressed by Schwann cells from normal nerves, axonal neuropathies and Schwannomas but their expression was low in MNST. VLA alpha5 was not expressed by Schwann cells from normal nerve and Schwannomas but present in chronic axonal neuropathies and MNST. In addition VLA alpha6 was strongly expressed by perineurial cells. These data show that CAMs have a characteristic pattern of expression in normal nerve. Also, some CAMs are always expressed by Schwann cells but the expression of others differs in normal nerves versus axonopathies or tumors, suggesting a role of the microcellular environment in the regulation of CAM expression. Schwannomas have different pattern of expression than MNST.

Axons↗
PubMed2003

Platelet adhesion to collagen and collagen-related peptide under flow: roles of the [alpha]2[beta]1 integrin, GPVI, and Src tyrosine kinases.

OBJECTIVE: Platelet stimulation by collagen and collagen-related peptides (CRPs) is associated with activation of protein tyrosine kinases. In the present study, we investigated the role of Src family tyrosine kinases in the initial adhesion events of human platelets to collagen and cross-linked CRP. METHODS AND RESULTS: Under arterial flow conditions, a glycoprotein VI-specific substrate, cross-linked CRP, caused rapid (<2 second) platelet retention and protein tyrosine phosphorylation that were markedly decreased by the Src family kinase inhibitor pyrozolopyrimidine (PP2) or by aggregation inhibitor GRGDSP. CRP-induced platelet retention was transient, and 90% of single platelets or aggregates detached within seconds. PP2, although having no effect on RGD peptide-binding to CRP, completely blocked aggregation and tyrosine phosphorylation of Syk and phospholipase Cgamma2 (PLCgamma2). In contrast, PP2 weakly (<30%) suppressed firm adhesion to collagen mediated primarily by the alpha2beta1 integrin. Although PP2 prevented activation of Syk and PLCgamma2 in collagen-adherent platelets, tyrosine phosphorylation of several unidentified protein bands persisted, as did autophosphorylation of pp125FAK. CONCLUSIONS: These findings indicate that activation of Src-tyrosine kinases Syk and PLCgamma2 is not required for the initial stable attachment of human platelets to collagen and for FAK autophosphorylation. However, Src-tyrosine kinases are critical for glycoprotein VI-mediated signaling leading to platelet aggregation.

Carrier Proteins↗
PubMed2002

The influence of platelet glycoprotein polymorphisms on receptor function and risk for thrombosis.

With regard to hemostasis and thrombosis, collagens are among the most important physiologic components of the extracellular matrix in their role as platelet activators. Differences in the rate of platelet activation markedly influence normal hemostasis and the pathological outcome of thrombosis. Thus, collagen receptors, such as the integrin alpha2beta1 and indirectly, GPIb alpha, represent a relatively unexploited target of pharmacological control and are only recently becoming appreciated as potential factors in the generic risk for thrombosis. In general, the importance platelet glycoprotein polymorphisms as genetic risk factors for arterial thrombosis is a new area of human genomics that needs to be carefully addressed. Discrepancies in the degree to which they are reported to contribute to risk for clinical thrombosis will only be resolved once there is a universal standard for clinical study design. Most of the clinical studies differ by patient population size, ethnicity, bias in the selection of patients and controls, plurality in clinical endpoints and variation of environmental factors. Despite these differences, there is substantial evidence that the integrin beta3 PlA2 haplotype, the GPIb alpha Met145 haplotype, the GPIb alpha -5C haplotype and the integrin alpha2 haplotype 1 (807T) each contribute to the risk for and morbidity of thrombotic disease. There may remain dispute as to the extent of their contribution. However, well-designed, large, prospective, genetic and epidemiologic studies are needed to clarify the role of these and other platelet receptor polymorphisms. Most importantly, the cumulative effects of multiple platelet and plasma glycoproteins SNPs to thrombotic risk must be evaluated concurrently. Additional in vitro studies of the functional relevance underlying these polymorphisms are needed to provide a sound biological explanation for the results of clinical correlations. The opportunity now exists to make significant inroads into the development of strategies for the prevention of thrombotic disease.

Genetic Predisposition to Disease↗
PubMed2006

Early steps in rotavirus cell entry.

Rotaviruses, the leading cause of severe dehydrating diarrhea in infants and young children worldwide, are non-enveloped viruses formed by three concentric layers of protein that enclose a genome of double-stranded RNA. These viruses have a specific cell tropism in vivo, infecting primarily the mature enterocytes of the villi of the small intestine. It has been found that rotavirus cell entry is a complex multistep process, in which different domains of the rotavirus surface proteins interact sequentially with different cell surface molecules, which act as attachment and entry receptors. These recently described molecules include integrins (alpha2beta1, alphavbeta3, and alphaxbeta2) and a heat shock protein (hsc70), and have been found to be associated with cell membrane lipid microdomains. The requirement for several cell molecules, which might need to be present and organized in a precise fashion, could explain the cell and tissue tropism of these viruses. This review focuses on recent data describing the interactions between the virus and its receptors, the role of lipid microdomains in rotavirus infection, and the possible mechanism of rotavirus cell entry.

Animals↗
PubMed2002

Regulatory effects of stem cell factor and interleukin-4 on adhesion of human mast cells to extracellular matrix proteins.

Mast cells are inflammatory and immunoregulatory cells resident in tissues. They develop from bone marrow-derived progenitor cells that enter the tissue through the blood circulation. The specific localization and migration of mast cells in tissues is dependent on their interaction with extracellular matrix (ECM) proteins. Adhesion of human mast cells isolated from intestinal mucosa and cultured in the presence of stem cell factor (SCF) to ECM proteins is analyzed. It was observed that SCF is a unique cytokine enhancing mast cell adhesion to all tested ECM proteins (fibronectin, laminin, collagen I, III, IV, VI, XIV) up to 5-fold, particularly to fibronectin (54% +/- 12% of mast cells) and to denatured collagens (40% +/- 12% on cyanogen bromide-cleaved peptides of collagen I). Most noteworthy, preculture of mast cells with interleukin-4 (IL-4), in addition to SCF, reduced their potency to adhere to ECM proteins to one third compared to mast cells cultured with SCF alone. Mast cell adhesion was preferentially mediated by beta1 integrins, and most cells expressed the ECM-binding integrins alpha2beta1, alpha3beta1, alpha4beta1, alpha5beta1, and alphaVbeta3. SCF-induced mast cell adhesion was totally blocked by wortmannin and apigenin, indicating an involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinase, and it was related to an up-regulation of the HUTS-21 beta1 epitope, which is associated with an activated conformation of beta1. In conclusion, these data indicate that SCF induces the adhesion of cultured mast cells to ECM proteins, whereas IL-4 may promote detachment from the ECM.

Cell Adhesion↗
PubMed2001

Platelet collagen receptors.

Collagens are important platelet activators in the vascular subendothelium and vessel wall. Since the regulation of platelet activation is a key step in distinguishing normal haemostasis from pathological thrombosis, collagen interactions with platelets are important targets for pharmacological control. Platelets have two major receptors for collagens, the integrin alpha2beta1, with a major role in adhesion and platelet anchoring and the Ig superfamily member, GPVI, principally responsible for signalling and platelet activation. In addition, GPIb-V-IX, can be considered as an indirect collagen receptor acting via von Willebrand factor as bridging molecule and is essential for platelet interactions with collagen at high shear rates. There is some evidence for additional receptors, which may regulate the response to individual collagen types. This review discusses how these receptors work separately with specific agonists and proposes possible mechanisms for how they work together to regulate platelet activation by collagen, which remains controversial and poorly understood.

Humans↗
PubMed2004

Novel signaling pathways mediating reciprocal control of keratinocyte migration and wound epithelialization through M3 and M4 muscarinic receptors.

To test the hypothesis that keratinocyte (KC) migration is modulated by distinct muscarinic acetylcholine (ACh) receptor subtypes, we inactivated signaling through specific receptors in in vitro and in vivo models of reepithelialization by subtype-selective antagonists, small interfering RNA, and gene knockout in mice. KC migration and wound reepithelialization were facilitated by M4 and inhibited by M3. Additional studies showed that M4 increases expression of "migratory" integrins alpha5beta1, alphaVbeta5, and alphaVbeta6, whereas M3 up-regulates "sedentary" integrins alpha2beta1 and alpha3beta1. Inhibition of migration by M3 was mediated through Ca2+-dependent guanylyl cyclase-cyclic GMP-protein kinase G signaling pathway. The M4 effects resulted from inhibition of the inhibitory pathway involving the adenylyl cyclase-cyclic AMP-protein kinase A pathway. Both signaling pathways intersected at Rho, indicating that Rho kinase provides a common effector for M3 and M4 regulation of cell migration. These findings offer novel insights into the mechanisms of ACh-mediated modulation of KC migration and wound reepithelialization, and may aid the development of novel methods to promote wound healing.

Animals↗
PubMed2001

The platelet receptor GPVI mediates both adhesion and signaling responses to collagen in a receptor density-dependent fashion.

The platelet response to collagen is a primary event in hemostasis and thrombosis, but the precise roles of the numerous identified platelet collagen receptors remain incompletely defined. Attention has recently focused on glycoprotein VI (GPVI), a receptor that is expressed on platelets in association with a signaling adapter, the Fc receptor gamma chain (Fc Rgamma). Genetic and pharmacologic loss of GPVI function results in loss of collagen signaling in platelets, but studies to date have failed to demonstrate that GPVI-Fc Rgamma expression is sufficient to confer collagen signaling responses. These results have led to the hypothesis that collagen responses mediated by GPVI-Fc Rgamma may require the collagen-binding integrin alpha2beta1 as a co-receptor, but this model has not been supported by a recent study of mouse platelets lacking alpha2beta1. In the present study we have used a novel anti-GPVI monoclonal antibody to measure the level of GPVI on human platelets and to guide the development of GPVI-expressing cell lines to assess the role of GPVI in mediating platelet collagen responses. GPVI receptor density on human platelets appears tightly regulated, is independent from the level of alpha2beta1 expression, and significantly exceeds that on previously characterized GPVI-expressing RBL-2H3 cells. Using newly generated GPVI-expressing RBL-2H3 cells with receptor densities equivalent to that on human platelets, we demonstrate that GPVI expression confers both adhesive and signaling responses to collagen in a graded fashion that is proportional to the GPVI receptor density. These results resolve some of the conflicting data regarding GPVI-collagen interactions and demonstrate that 1) GPVI-Fc Rgamma expression is sufficient to confer both adhesion and signaling responses to collagen, and 2) GPVI-mediated collagen responses are receptor density-dependent at the receptor levels expressed on human platelets.

3T3 Cells↗
PubMed2005

Function of discoidin domain receptor I in HGF-induced branching tubulogenesis of MDCK cells in collagen gel.

Discoidin domain receptor I (DDR1) is a receptor tyrosine kinase (RTK) and serves as the receptor for collagen in addition to integrins. It has been well established that Madin-Darby canine kidney (MDCK) cells develop branching tubules in three-dimensional collagen gel in the presence of hepatocyte growth factor (HGF). MDCK cells normally express DDR1. However, the function of DDR1 in this in vitro model system has not been understood. We established stable-transfected MDCK cells harboring DDR1a, DDR1b, or dominant-negative (DN) DDR1 and cultured these transfectants in collagen gel with HGF (2 ng/ml) for the studies of branching tubule morphogenesis. Whether DDR1 played roles in cell growth, apoptosis, and migration was examined. We found that cells over-expressing DDR1a and DDR1b developed shorter tubules with fewer branches in collagen gel. In contrast, DN DDR1 over-expressed cells could not form tubule structure, but instead developed mostly cell aggregates with multiple long extended processes. Over-expression of DDR1a and 1b in MDCK cells resulted in reduction of cell growth when cells were cultured on collagen gel-coated dishes or collagen gel. On the other hand, DN DDR1 enhanced cell death on collagen gel, suggesting that DDR1 is involved in maintenance of cell survival. Moreover, over-expression of DDR1a and DDR1b markedly reduced collagen-induced migration capability, whereas DN DDR1 enhanced it, suggesting that DDR1a and 1b may serve as a negative regulator for alpha2beta1 integrin during migration on collagen substratum. These results indicate that DDR1 plays important role in regulation of HGF-induced branching tubulogenesis by modulating cell proliferation, survival, and cell migration.

Animals↗
PubMed1999

Evidence for the involvement of p59fyn and p53/56lyn in collagen receptor signalling in human platelets.

The binding of collagen to platelet glycoprotein VI (GPVI) leads to the subsequent activation of phospholipase Cgamma2 through a pathway that is dependent on the Fc receptor gamma (FcR gamma) chain and the tyrosine kinase p72syk. We have investigated the role of platelet Src-family kinases in this signalling pathway. The selective Src-family kinase inhibitor PP1 prevented collagen-stimulated increases in whole-cell tyrosine phosphorylation and tyrosine phosphorylation of the FcR gamma chain and p72syk. A similar set of observations was made for a collagen-related peptide (CRP), which binds to GPVI but not to the integrin alpha2beta1 (GPIa/IIa). These effects were seen at a concentration of PP1 that inhibited platelet aggregation, dense granule release and Ca2+ mobilization induced by CRP, but not aggregation and Ca2+ mobilization mediated by the G-protein-coupled receptor agonist thrombin. After stimulation by CRP or collagen, the Src-family kinases p59fyn and p53/56lyn became associated with several tyrosine-phosphorylated proteins including the FcR gamma chain. This was not true of the other platelet Src-family kinases. The association between the FcR gamma chain and p59fyn was also seen under basal conditions, and was stable only in the weak detergent Brij96 but not in Nonidet P40, suggesting a non-SH2-dependent interaction. These results provide strong evidence for the involvement of p59fyn and p53/56lyn in signalling via GPVI, with p59fyn possibly acting upstream of FcR gamma chain phosphorylation.

Blood Platelets↗
PubMed1997

Immunohistochemical expression and distribution of alpha2beta1, alpha6beta1, alpha5beta1 integrins and their extracellular ligands, type IV collagen, laminin and fibronectin in palmar fibromatosis.

Palmar fibromatosis is characterized by changes in the expression of extracellular matrix (ECM) proteins and re-organization of the interactions between cellular and extracellular compartments. We compared the expression and distribution of alpha2beta1, alpha6beta1, alpha5beta1 integrins and their corresponding extracellular ligands, type IV collagen, laminin and fibronectin in palmar fibromatosis nodules from 24 patients. Depending on the degree of cellularity and fibrosis, three different histologic phases were identified: proliferative, involutional, and residual. Immunohistochemistry revealed that only stromal cells of the highly cellular areas of both proliferative and involutional phases were myofibroblasts, as demonstrated by their cytoplasmic positivity for alpha-smooth-muscle actin. The ECM, surrounding these cells, was strongly and diffusely positive to type IV collagen, laminin and fibronectin, whereas no immunoreactivity was found in the ECM of the fibrotic and hypocellular areas of both involutional and residual phases. Immunostaining for alpha2beta1, alpha6beta1 and alpha5beta1 integrins revealed that alpha5beta1 integrin was expressed and restricted to the myofibroblast-rich cellular areas, whereas no expression was detected for alpha2beta1 and alpha6beta1 integrins. By examining serial sections, a co-localization of alpha5beta1 integrin and fibronectin was observed in the myofibroblast-rich cellular areas, indicating that, in palmar fibromatosis, a co-ordinate expression between cellular and extracellular ligand is detected only for the alpha5beta1 integrin/fibronectin complex. These findings suggest that the alpha5beta1 integrin/fibronectin complex may be involved in regulating the interactions between myofibroblasts and ECM in palmar fibromatosis.

Actins↗