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PubMed2004

Expression of {beta}1 integrin receptors during rat pancreas development--sites and dynamics.

The integrin receptors link to extracellular matrix proteins and exert a dynamic role in development by providing the physical basis for cell adhesion and controlling cell growth. In the present study, we examined changes in the expression of beta1 integrins and its associated alpha-subunits to islet cell development in the rat pancreas. A significant increase in protein expression of integrin alpha3, alpha6, and beta1 was observed from fetal to postnatal life. High mRNA levels of these integrin subunits was detected at embryonic d 18 and dropped significantly after birth with relatively low expression throughout postnatal life. Integrins alpha3, alpha5, alpha6, and beta1 were expressed in a cell-specific manner in the pancreas with high integrin immunoreactivity in duct and islet regions during fetal life, and a progressive increase later into postnatal life. The coexpression with islet and putative islet precursor markers during fetal and postnatal development suggest a role for these integrin subunits in differentiation and maturation of islets. Functional studies in vitro showed that anti-beta1 antibody treatment inhibited islet cell adhesion to extracellular matrices and disrupted islet architecture. Blockade of beta1 integrin receptor and knockdown beta1 mRNA resulted in a decrease in the expression of insulin mRNA and increased islet cell death. These results suggest that progression in islet cell development is accompanied by and dependent upon cell adhesion via beta1 integrin and its respective alpha-subunits and suggest that the beta1 family of integrins may play a critical role in islet cell architecture, development, integrity, and function.

Animals↗

PubMed2005

Integrin alpha3beta1 suppresses long-term potentiation at inhibitory synapses on the cerebellar Purkinje neuron.

At the GABAergic synapses between inhibitory interneurons and a Purkinje neuron (PN) in the cerebellum, the postsynaptic depolarization induces the long-term potentiation (called rebound potentiation; RP) of GABAA receptor responsiveness. Here, we show that integrins, a type of cell-adhesion molecules, are involved in the regulation of RP. Integrin activation by Mn2+ impaired the RP induction of GABA responsiveness and mIPSCs in PNs, which was abolished by the function blocking antibody against either integrin alpha3 or beta1 subunit, but not by that against alpha5 or alphaV subunit. Furthermore, overexpression of integrin alpha3 subunit in a PN by itself impaired the RP induction. We also show that Src-family of protein tyrosine kinases mediated the suppressive effect of integrin activity on the RP induction. Thus, the integrin/Src pathway negatively regulates the induction of long-term plasticity at inhibitory synapses on a cerebellar PN.

Animals↗

PubMed1997

Integrin alpha chain cytoplasmic tails regulate "antibody-redirected" cell adhesion, independently of ligand binding.

Here we describe a novel "antibody-redirected cell adhesion" (ARCA) assay. This assay measures heterotypic cell-cell adhesion, resulting from antibody bridging between Fc gamma receptors type II (CD32) on leukocytes, and clustered integrins on adherent cell monolayers. This ARCA activity, facilitated by integrins alpha3 beta1 or alpha4 beta1, required an intact cytoskeleton, but did not involve typical integrin ligand binding sites or divalent cations. Furthermore, deletion of the alpha4 cytoplasmic tail almost completely abrogated integrin ARCA activity, suggesting an alteration of integrin recruitment into adhesive sites. If two or more tail residues were present after the conserved GFFKR motif, then ARCA activity was largely restored. Although alpha4 tail deletion caused loss of ARCA activity, it had no effect on the binding of VCAM-1 to intact alpha4-transfected K562 cells. In conclusion, the integrin alpha chain tail can positively regulate integrin-dependent cell adhesion by a receptor recruitment/clustering mechanism independent of conventional integrin ligand-binding considerations.

Actin Cytoskeleton↗

PubMed2003

None of the integrins known to be present on the mouse egg or to be ADAM receptors are essential for sperm-egg binding and fusion.

Antibody inhibition and alpha6beta1 ligand binding experiments indicate that the egg integrin alpha6beta1 functions as a receptor for sperm during gamete fusion; yet, eggs null for the alpha6 integrin exhibit normal fertilization. Alternative integrins may be involved in sperm-egg binding and fusion and could compensate for the absence of alpha6beta1. Various beta1 integrins and alphav integrins are present on mouse eggs. Some of these integrins are also reported to be receptors for ADAMs, which are expressed on sperm. Using alpha3 integrin null eggs, we found that the alpha3beta1 integrin was not essential for sperm-egg binding and fusion. Oocyte-specific, beta1 integrin conditional knockout mice allowed us to obtain mature eggs lacking all beta1 integrins. We found that the beta1 integrin null eggs were fully functional in fertilization both in vivo and in vitro. Furthermore, neither anti-mouse beta3 integrin function-blocking monoclonal antibody (mAb) nor alphav integrin function-blocking mAb inhibited sperm binding to or fusion with beta1 integrin null eggs. Thus, function of beta3 or alphav integrins does not seem to be involved in compensating for the absence of beta1 integrins. These results indicate that none of the integrins known to be present on mouse eggs or to be ADAM receptors are essential for sperm-egg binding/fusion, and thus, egg integrins may not play the role in gamete fusion previously attributed to them.

ADAM Proteins↗

PubMed2003

Regulation of epithelial cell cytokine responses by the alpha3beta1 integrin.

Epithelial cells (EC) from various tissues can produce important cytokines and chemokines when stimulated by proinflammatory cytokines. These EC also receive signals from cell surface integrins, like the alpha3beta1 integrin, which is important in cell migration and wound healing of epithelial monolayers. However, little is known of the effect of integrin signals on cytokine responses by EC. Colonic Caco-2 cells treated with an anti-alpha3 integrin antibody prior to stimulation with the proinflammatory cytokine interleukin (IL)-1 yielded suppressed levels of mRNA and secreted IL-6, IL-8 and monocyte chemoattractant protein-1 as compared to cells treated with normal mouse immunoglobulin G. Lung A549 cells also showed a similar suppression of cytokine secretion. Likewise, treatment of the Caco-2 cells with the same antibody suppressed tumour necrosis factor-alpha-stimulated IL-6 secretion. Fab fragments of the anti-alpha3 integrin antibody did not induce the suppressive effect but did block the suppressive effect of the whole antibody suggesting that the effect of the antibody required cross-linking of the integrins. Finally, culture of the Caco-2 cells on laminin type 5 (the major ligand for this integrin) yielded depressed levels of IL-1-induced IL-6 secretion as compared to cells on laminin type 1. These data are the first indication that the alpha3beta1 integrin may cause a suppression of cytokine responses by EC which may be important in regulating the capacity of EC to respond during inflammation or wound healing.

Antibodies, Monoclonal↗

PubMed2004

[Dynamic changes in focal adhesion kinase during cell migration induced by bFGF and the significance].

Cell migration plays an important role in repair of injury, angiogenesis, cancer metastasis and so on. In this paper the effects of basic fibroblast growth factor (bFGF) of different concentrations on ECV-304 cell migration, and the dynamic changes in focal adhesion kinase (FAK) were observed. The relationship between FAK and cell migration induced by bFGF was studied. A ECV-304 cell scratch wound model was established and the images of cell migration were quantitatively measured using a computer-assisted videomicroscopic system. The dynamic changes in FAK content (Western blot), FAK activity (immunoprecipitation plus Western blot) and FAK mRNA (RT-PCR) were measured in vitro. The expression of integrin alpha3 was investigated using immunocytochemical staining (ABC method). The results showed that bFGF produced a dual-phase regulatory effect on ECV-304 migration when the cell confluent areas reached 90%-95% in culture. It was found that compared with the control group (0 ng/ml bFGF), the cell migration was stimulated (P<0.05), inhibited (P<0.05) and unchanged when the cultured cells were treated with bFGF at the concentrations of 5, 10 and 15 ng/ml, respectively. The content and activity of FAK protein were markedly up-regulated in 5 ng/ml bFGF group and down-regulated in 15 ng/ml bFGF group, respectively. FAK mRNA expression came to the peak in 5 ng/ml bFGF group after 6 h culture and there was a significant difference compared with the control group. In various experimental groups there were no significant differences in the expression of integrin alpha3 compared with the control group according to the immunocytochemical staining. The results mentioned above suggest that different concentrations of bFGF have a dual-phase effect on the migration of cultured ECV-304 cells, which correlates positively with FAK content, activity and mRNA in cultured ECV-304 cell scratch wound model. The FAK plays an important role in the signal transduction pathway of cell migration induced by bFGF, while bFGF can regulate the content of FAK in ECV-304 cells at gene transcription level.

Cell Movement↗

PubMed2000

Function of fusion regulatory proteins (FRPs) in immune cells and virus-infected cells.

Two molecules that regulate cell fusion have been identified and designated fusion regulatory protein-1 (FRP-1) and FRP-2. FRP-1 is a complex composed of a glycosylated heavy chain and a nonglycosylated light chain that are disulfide linked. FRP-1 heavy chain is identical to 4F2/CD98 heavy chain, whereas FRP-2 is identical to integrin alpha3 subunit. The FRP-1 heavy chain is a multifunctional molecule: that is, fusion regulator, amino acid transporter, integrin regulator, comitogenic factor, Na+-Ca2+ exchanger, oncogenic protein, and so on. Several aspects of the structure and function of the FRP-1 system are reviewed: fusion regulatory molecular mechanisms, cross-talk between the FRP-1 and integrin, the FRP-1 system as amino acid transporter, and FRP-1-mediated T-cell activation. The FRP-1 system is involved in virus-mediated cell fusion and multinucleated giant cell formation of blood monocytes. Monoclonal antibodies against human FRP-1 heavy chain induce polykaryocytes that have properties as osteoclasts. Multiple steps participate in molecular mechanisms regulating cell fusion. The FRP-1 heavy chain supports amino acid transport activity and the FRP-1 light chains have recently been cloned as amino acid transporters that require association with the heavy chain to exhibit their activity. Novel pathways for monocyte-dependent regulation of T-cell activation have recently been found that are mediated by the FRP-1 system. In conclusion, the FRP-1 molecules are essential factors for basic cellular functions.

Amino Acids↗

PubMed2001

Transmembrane-4 superfamily proteins associate with activated protein kinase C (PKC) and link PKC to specific beta(1) integrins.

Translocation of conventional protein kinases C (PKCs) to the plasma membrane leads to their specific association with transmembrane-4 superfamily (TM4SF; tetraspanin) proteins (CD9, CD53, CD81, CD82, and CD151), as demonstrated by reciprocal co-immunoprecipitation and covalent cross-linking experiments. Although formation and maintenance of TM4SF-PKC complexes are not dependent on integrins, TM4SF proteins can act as linker molecules, recruiting PKC into proximity with specific integrins. Previous studies showed that the extracellular large loop of TM4SF proteins determines integrin associations. In contrast, specificity for PKC association probably resides within cytoplasmic tails or the first two transmembrane domains of TM4SF proteins, as seen from studies with chimeric CD9 molecules. Consistent with a TM4SF linker function, only those integrins (alpha(3)beta(1), alpha(6)beta(1), and a chimeric "X3TC5" alpha(3) mutant) that associated strongly with tetraspanins were found in association with PKC. We propose that PKC-TM4SF-integrin structures represent a novel type of signaling complex. The simultaneous binding of TM4SF proteins to the extracellular domains of the integrin alpha(3) subunit and to intracellular PKC helps to explain why the integrin alpha3 extracellular domain is needed for both intracellular PKC recruitment and PKC-dependent phosphorylation of the alpha(3) integrin cytoplasmic tail.

Animals↗

PubMed2000

Glycosylation affects translocation of integrin, Src, and caveolin into or out of GEM.

Endogenous GM3 synthesis and full N-glycosylation in membrane receptors occurred in "4-epimerase-less" ldlD (Krieger's CHO mutant) cells cultured in Gal-containing medium, whereby components of detergent-insoluble, low-density, buoyant membrane fraction, termed "glycolipid-enriched microdomain (GEM)," varied significantly by translocation into or out of GEM. Integrins alpha3 and alpha5 were translocated into GEM in the presence of 0.5 or 0.25% Triton X-100, particularly in the absence of Gal, whereby integrins are underglycosylated and GlcCer is the major glycolipid component in GEM. Src family kinase was translocated into and enriched in GEM fractions when prepared in 0.5 or 0.25% Triton X-100 from cells grown in Gal-containing medium, whereby GM3 synthesis is induced. In contrast, caveolin is highly enriched in GEM when GM3 synthesis does not occur, and is translocated into high-density membrane fraction when GM3 synthesis occurs. The results suggest that levels of key molecules controlling cell adhesion and signaling are defined by translocation into or out of GEM, which depends on glycosylation state.

Animals↗

PubMed1997

Cloning and characterization of cDNAs encoding the integrin alpha2 and alpha3 subunits from Xenopus laevis.

Integrins containing the alpha2 and alpha3 subunits associate with the beta1 subunit to form distinct receptors with partially overlapping adhesive specificities. We report the cloning and sequence of cDNAs that encode the Xenopus orthologues of integrins alpha2 and alpha3 and the expression of these subunits during embryogenesis. Integrin alpha2 and alpha3 mRNAs are first expressed in the dorsal mesoderm and developing notochord at gastrulation. We also show that alpha3 mRNAs are expressed in the entire marginal zone of gastrulae dorsalized with LiCl but that this localization is lost in embryos ventralized by ultraviolet light. Immunoblots reveal that the alpha3 protein is expressed throughout early development, however, the alpha2 protein is not detected until late tailbud stages. Injection of full-length alpha3 transcripts into the animal poles of fertilized eggs results in embryonic defects in paraxial mesoderm attributed to the failure of somites to form segments. Injection of the alpha3 transcripts into the vegetal pole and overexpression of a 5'-truncated alpha3 control construct have no apparent affect on development or somite formation. These data suggest that normal position-specific expression of integrins is important in maintaining the proper organization of tissues during early amphibian morphogenesis.

Amino Acid Sequence↗

PubMed2005

Laminin-5-integrin interaction signals through PI 3-kinase and Rac1b to promote assembly of adherens junctions in HT-29 cells.

Human intestinal cell differentiation is mediated by signaling pathways that remain largely undefined. We and others have shown that cell migration and differentiation along the crypt-villus axis is associated with temporal and spatial modulations of the repertoire, as well as with the function of integrins and E-cadherins and their substrates. Cross-talk between integrin and cadherin signaling was previously described and seems to coordinate this differentiation process. Here, we report that engagement of alpha6 and, to a lesser extent, alpha3 integrin subunits after HT-29 cell adhesion on laminin 5 increases the expression of E-cadherin, which then organizes into nascent adherens junctions. We further identify that phosphoinositide 3-kinase (PI 3-kinase) activation plays a key role in this cross-talk. Indeed, integrin-dependent adhesion on laminin 5 stimulates PI 3-kinase activity. Immunofluorescence and immunoprecipitation experiments revealed that activated PI 3-kinase is recruited at cell-cell contacts. Using LY294002, an inhibitor of PI 3-kinase activity, we found that this activation is essential for E-cadherin connection with the cytoskeleton and for biogenesis of adherens junctions. Finally, we demonstrated that PI 3-kinase could signal through Rac1b activation to control adherens junction assembly. Our results provide a mechanistic insight into integrin-cadherin cross-talk and identify a novel role for PI 3-kinase in the establishment of adherens junctions.

Adherens Junctions↗

PubMed2005

alpha3beta1 integrin induced suppression of the Caco-2 epithelial cell IL-1 signaling pathway leading to NF-(kappa)B activation.

Intestinal epithelial cells (IECs) produce several potent cytokines in response to interleukin-1 (IL-1) and may play a role in the inflammatory response. Previously, we determined that treatment of the Caco-2 cells with a cross-linking anti-alpha3 integrin antibody resulted in a suppression of IL-1 induced cytokine secretion and mRNA levels, suggesting that the alpha3beta1 integrin may play a role in the regulation of IEC cytokine responses to IL-1. In this report, treatment of the Caco-2 cells with the anti-alpha3 integrin antibody resulted in a suppression of IL-1 induced levels of NF-kappaB binding activity in nuclear extracts, as determined by EMSA, as well as phosphorylation and degradation of the inhibitor, I(kappa)B(alpha). The anti-integrin antibody treatment was also found to suppress I(kappa)B kinase (IKK) activity and IKK(beta) phosphorylation. Culture of the Caco-2 cells on purified laminin-5, the ligand for the alpha3beta1 integrin, also resulted in suppression of IL-1 induced phosphorylation of I(kappa)B(alpha) and IKK(beta). Together with our previous findings, these results suggest that alpha3beta1 integrin binding results in a suppression of the IL-1 signaling pathway leading to the activation of NF-(kappa)B and ultimately IEC cytokine responses. These studies define a novel regulatory mechanism which may be important in the control of IEC cytokine responses during inflammation.

Antibodies↗

PubMed2003

Identification of potential biomarkers of lymph node metastasis in oral squamous cell carcinoma by cDNA microarray analysis.

We surveyed the expression of 557 cancer-related genes in 15 cases of well-differentiated OSCC by cDNA microarray analysis. To identify potential biomarkers for lymph node metastasis, all microarray data were compared by the Mann-Whitney test and the significance analysis of microarrays between OSCCs with and those without lymph node metastasis. The tissues of OSCCs with lymph node metastasis exhibited increased expression levels of MMP-1, MMP-3, uPA, integrin-alpha3, paxillin, tenascin C and IL-6 transcripts. All of these genes were included in common clusters on the Cluster/TreeView analysis, implying that functional gene groups of proteolytic enzymes and integrin-related molecules are involved in cervical lymph node metastasis. The results of RTQ-PCR for differentially expressed genes were in accord with those of cDNA microarray analyses, suggesting that the data obtained by microarray gene expression analyses were valid. Consistent with cooperative expression patterns, immunohistochemical analyses demonstrated that products of MMP-1, MMP-3 and uPA were colocalized to components of the neoplastic stroma, particularly mononuclear inflammatory cells with well-developed eosinophilic cytoplasm. Our results suggest that expression levels of molecules involved in tissue remodeling and cell-ECM adhesion, especially MMP-1 and integrin-alpha3, can provide an accurate biomarker system for predicting the risk of cervical lymph node metastasis in OSCC.

Biomarkers, Tumor↗

PubMed2002

Differential expression of collagen integrin receptor on fetal vs. adult skin fibroblasts: implication in wound contraction during healing.

BACKGROUND: Fetal skin wound healing is characterized by an absence of contraction and scar formation, two important observations associated with adult healing often leading to pathological problems. OBJECTIVES: We have studied the capacity of adult and fetal human skin fibroblasts to contract collagen gels, collagen being the major structural component of dermal matrix. METHODS: In parallel with collagen gel contraction studies, we have used fluorescence-activated cell sorter analysis to study the levels of collagen receptors expressed at the surface of fibroblasts derived from fetal or adult skin samples. RESULTS: Strong differences were detected between freshly isolated fetal and adult fibroblasts. Fetal fibroblasts had a very low capacity to contract collagen gel, whereas adult cells significantly contracted gels in the same conditions. The expression of alpha1, alpha2 and alpha3 integrin subunits was also significantly different depending of the donor age: alpha1 and alpha3 integrin subunit expression was lower in fetal cells compared with adult cells, whereas alpha2 integrin subunit expression was higher. When grown in monolayers, adult cells showed rapid changes in their contractile capacity and integrin expression while fetal cells were only affected after several passages. CONCLUSIONS: These observations indicate that intrinsic differences between fetal and adult fibroblasts can strongly influence the quality of wound repair.

Adolescent↗

PubMed1998

Differential effects of integrin alpha chain mutations on invasin and natural ligand interaction.

To determine if recognition of the Yersinia pseudotuberculosis invasin protein and natural substrates requires identical integrin residues, a region of the human alpha3 integrin chain predicted to be involved in substrate adhesion was targeted for mutation. One point mutation located in a region of the third N-terminal repeat of the alpha3 chain, alpha3-W220A, failed to promote adhesion to the natural alpha3 beta1 substrate epiligrin but maintained near wild type levels of adhesion to invasin. A second nearby mutation, alpha3-Y218A, which showed no detectable adhesion to epiligrin, was only partially attenuated for invasin binding as well as invasin-mediated bacterial uptake. A third substitution, alpha3-D154A, predicted to be in the second N-terminal repeat not known to be implicated in cell adhesion, was competent for invasin-promoted adhesion events and appeared to encode a receptor of increased activity, as it had a higher efficiency than wild type receptor for adhesion to epiligrin. Cell lines expressing this derivative were not recognized by a function blocking anti-alpha3 antibody, indicating that the second and third repeats of the alpha3 chain are either closely linked in space or the second repeat can modulate activity of the third. Differential effects on substrate adhesion do not appear to be associated with all integrin alpha chain mutations, as alpha4 chain mutations affecting the divalent cation binding domains depressed adhesion to invasin to a significant extent.

Adhesins, Bacterial↗

PubMed2004

Expression of integrin subunits alpha2, alpha3, alpha5, alphav, beta1, beta3 and beta4 in different histological types of ameloblastoma compared with dental germ, dental lamina and adult lining epithelium.

OBJECTIVE: To analyze integrin expression and distribution in different histological types of ameloblastoma, compared with dental germ, dental lamina and adult lining epithelium. MATERIALS AND METHODS: Three-micrometer sections from paraffin-embedded specimens were evaluated employing a streptavidin-biotin immunohistochemical method and anti-integrin alpha2, alpha3, alpha5, alphav, beta1, beta3 and beta4 antibodies. RESULTS: All integrins were present in all specimens, exhibiting different patterns. In follicular ameloblastoma, the integrin staining was stronger in the periphery while integrin alpha2 was not present in the central cells. Acanthomatous ameloblastoma showed a similar pattern, with positive staining for integrins alpha3, alpha5, alphav, beta1 and beta4 in the metaplastic cells. In the unicystic, integrin staining was uniform except for integrins alpha5 and beta3 which showed weaker staining in the upper layers. In the plexiform ameloblastoma, dental germ and lamina integrin staining was uniform. In the adult lining epithelium, staining for integrins alpha2, alpha5 and beta4 was confined to the basal layer, while integrins alphav and beta3 were present in the basal and parabasal, with integrins alpha3 and beta1 in the upper layers. CONCLUSION: Acanthomatous, follicular and unicystic ameloblastomas showed integrin staining patterns similar to the adult lining epithelium while the plexiform ameloblastoma was similar to the dental germ and lamina.

Adult↗

PubMed2006

The inhibition of tumor cell adhesion on human mesothelial cells (HOMC) by phospholipids in vitro.

BACKGROUND AND AIMS: Intraperitoneal tumor cell adhesion to extracellular matrix and to mesothelial cells mediated by integrins is an important step in developing peritoneal carcinosis. In former animal studies, we could demonstrate that intraperitoneal treatment with a new phospholipid (PL) emulsion significantly reduces the amount of peritoneal carcinosis by adhesion prevention. This in vitro study tries to elucidate the influence of phospholipids on cells of the human gastric cancer cell line (NUGC-4) and the human rectal cancer cell line (HRT-18) adhering to mesothelial cells (HOMC) in a monolayer culture in vitro. MATERIALS AND METHODS: HOMC cells were derived from omentum majus from patients undergoing elective abdominal surgery. Three passages of both cancer cell lines (NUGC-4 and HRT-18) were used. 1x10(5)/100 microl (HRT-18) or 1.2x10(5)/100 microl (NUGC-4) cells, according to forgoing dilution series, were pretreated with different concentrations of phospholipid emulsion (0.05, 0.1, 0.5, 0.75, 1% PL) stained with cell tracker chloromethyl-benzamidodialkylcarbocyanine (CM-DIL) and seeded into each well on the mesothelial monolayer. After 90 min, the number of adherent cells was counted by fluorescence microscopy at 530 and 620 nm. Additionally, flow cytometric analysis of integrin alpha3 and beta1 expression on the tumor cell surface after treatment with phospholipids was completed. RESULTS: We found a dose dependent effect of phospholipids on both tumor cell lines causing a reduction of cell-cell adhesion. Already low concentrations of phospholipids (PL 0.5) had a significant influence. The mean cell count could be reduced from 234+/-12/mm2 in controls to 124+/-41/mm2 (PL 0.5; NUG-4) and from 295+/-49/mm2 to 169+/-29/mm2 (PL 0.5; HRT-18), respectively. Additionally, the integrin alpha3 and beta1 expression on both cell lines could be reduced. CONCLUSION: Our results within the scope of published data indicate that adhesion prevention is capable to reduce peritoneal carcinosis.

Anticarcinogenic Agents↗

PubMed2000

Integrin expression during epithelial migration and restratification in the tenascin-C-deficient mouse cornea.

In the unwounded cornea, tenascin-C localizes to a short stretch of the basement membrane zone at the corneoscleral junction or limbus. To determine whether the function of the limbus is affected by the absence of tenascin-C, mice possessing a deletion of tenascin-C and strain-matched wild-type mice are used in corneal debridement wounding experiments. The expression of integrins (alpha3, alpha9, and beta4) in the tenascin-C knockout corneas is evaluated by producing polyclonal cytoplasmic domain antipeptide sera and performing immunofluorescence microscopy. In addition, we evaluate the localization of several other proteins involved in wound healing, including fibronectin, laminin beta1, nidogen/entactin, and VCAM-1, in both the tenascin knockout and wild-type mice. There are no differences in healing rate, scarring, or neovascularization after corneal debridement wounds. alpha9 integrin is expressed at the limbal border of unwounded tenascin-C knockout animals and is upregulated during migration only after the larger wounds. At 8 weeks after larger wounds, the localization of alpha9 again becomes restricted to the limbal border. Results show that tenascin-C is not required for development or maintenance of the corneal limbus or for normal re-epithelialization of corneal epithelial cells after debridement wounding.

Animals↗