SEARCH · PubMed Health

Results for “Integrin alpha5”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1998

Dystrophic muscle in mice chimeric for expression of alpha5 integrin.

alpha5-deficient mice die early in embryogenesis (). To study the functions of alpha5 integrin later in mouse embryogenesis and during adult life we generated alpha5 -/-;+/+ chimeric mice. These animals contain alpha5-negative and positive cells randomly distributed. Analysis of the chimerism by glucose- 6-phosphate isomerase (GPI) assay revealed that alpha5 -/- cells contributed to all the tissues analyzed. High contributions were observed in the skeletal muscle. The perinatal survival of the mutant chimeras was lower than for the controls, however the subsequent life span of the survivors was only slightly reduced compared with controls (). Histological analysis of alpha5 -/-;+/+ mice from late embryogenesis to adult life revealed an alteration in the skeletal muscle structure resembling a typical muscle dystrophy. Giant fibers, increased numbers of nuclei per fiber with altered position and size, vacuoli and signs of muscle degeneration-regeneration were observed in head, thorax and limb muscles. Electron microscopy showed an increase in the number of mitochondria in some muscle fibers of the mutant mice. Increased apoptosis and immunoreactivity for tenascin-C were observed in mutant muscle fibers. All the alterations were already visible at late stages of embryogenesis. The number of altered muscle fibers varied in different animals and muscles and was often increased in high percentage chimeric animals. Differentiation of alpha5 -/- ES cells or myoblasts showed that in vitro differentiation into myotubes was achieved normally. However proper adhesion and survival of myoblasts on fibronectin was impaired. Our data suggest that a novel form of muscle dystrophy in mice is alpha5-integrin-dependent.

Animals↗

PubMed1998

Identification of a domain on the integrin alpha5 subunit implicated in cell spreading and signaling.

The alpha5 beta1 integrin is a cell surface receptor for fibronectin implicated in several cellular activities including cell proliferation, differentiation, and migration. The primary site at which the alpha5 beta1 integrin interacts with fibronectin is the RGD (Arg-Gly-Asp) amino acid sequence. In general, the sites on the integrin alpha subunits involved in ligand binding are not well characterized. Based on previous cross-linking studies, sequence alignment, predicted conformation, and intron-exon boundaries, we identified a 144-residue region (positions 223-367) on the alpha5 subunit as a putative binding region and divided it into four subdomains named domains I, II, III, and IV. Chimeric receptors were prepared in which sequences on the alpha5 subunit were exchanged with the corresponding sequences on the alpha6 subunit, which is specific for laminin and does not bind via an RGD sequence. The mutated human alpha5 integrin gene was transfected into CHO B2 cells, which are deficient in alpha5 expression. Only chimeras of domain III or IV express on the cell surface. Both of these chimeras decreased the adhesion, spreading, focal adhesion assembly, and migration on fibronectin. The adhesion of the chimeric receptors to fibronectin remained sensitive to the RGD peptide, and antibodies that inhibit interaction with the fibronectin synergy site and RGD loop remain inhibitory for the chimeras, indicating that our chimeras do not inhibit binding to either the RGD or synergy sites. Finally, the affinity of soluble fibronectin to cells via the alpha5 beta1 receptor decreased only about 3-fold. This decrease is substantially less than the observed effects on migration and spreading, which were not altered by changes in substrate concentration. Thus, the alteration in binding sites does not easily account for the changes in cell spreading and focal adhesion assembly. The tyrosine phosphorylation and focal adhesion assembly that are seen when cells expressing the wild type alpha5 receptor adhere to fibronectin were inhibited in cells expressing the chimeric receptors. Therefore, our results suggest that the chimeras of these domains likely interrupt alpha5-mediated conformational signaling.

Amino Acid Sequence↗

PubMed2000

Significance of integrin alpha5 gene expression as a prognostic factor in node-negative non-small cell lung cancer.

The integrin family plays a major role in complex biological events such as differentiation, development, wound healing, and the altered adhesive and invasive properties of tumor cells. Integrin (alpha5beta1 is a classical fibronectin receptor, and it has been known as a tumor suppressor gene because tumor cells overexpressing alpha5beta1 are less tumorigenic than their parent cells. However, this finding conflicts with some recent data that suggests that the emergence of alpha5beta1 expression correlates with the tumor progression. We, therefore, investigated the expression of alpha5beta1 integrin in 20 lung cancer cell lines by flow cytometric analysis and in 88 node-negative non-small cell lung cancers (NSCLCs) by RT-PCR and immunohistochemical assays to determine the significance of this prognostic factor. In the 20 lung cancer cell lines, 8 (40.0%) cell lines strongly expressed integrin alpha5, 3 (15.0%) cell lines had moderate or weak alpha5 expression, and the remaining 9 (45.0%) cell lines expressed no integrin alpha5. In the 88 node-negative NSCLC patients, 44 samples (50.0%) were evaluated as having integrin alpha5 overexpression, and the integrin alpha5 expression was significantly associated with the status of differentiation and the age of the patients (P = 0.0379 and 0.0312, respectively). In the node-negative patients, the overall survival rate for patients with integrin alpha5 overexpressed tumors was significantly worse than for those individuals whose tumors had normal integrin alpha5 expression (P = 0.016).

Aged↗

PubMed1997

Integrin alpha5 is expressed on human luteinizing granulosa cells during corpus luteum formation, and its expression is enhanced by human chorionic gonadotrophin in vitro.

We previously reported that human granulosa cells (GC) express integrin alpha6beta1, in large follicles and early corpus luteum (CL). In this study, we examined the expression of integrin alpha5 and fibronectin (FN) by immunohistochemistry. Integrin alpha5 was undetectable on human GC in preovulatory follicles, but it was intensely expressed on luteinizing GC of CL in the early luteal phase, and it was weakly expressed on large luteal cells (LL) in the midluteal phase. FN was similarly expressed between GC/LL. Thus, integrin alpha5 and FN were stage-specifically expressed on/between luteinizing GC in the early luteal phase. Next we examined the effect of human chorionic gonadotrophin (HCG) on expression of integrin alpha5 on luteinizing GC in vitro. GC obtained from preovulatory follicles were cultured for 3 days without (control) or with HCG (1 IU/ml), and expression of integrin alpha5 was examined by flow cytometry. Although the positivity rate did not differ, the mean relative fluorescence intensity was 3.4-fold higher in the HCG-treated group (n = 8, P < 0.01). These findings indicate that integrin alpha5 is rapidly expressed on GC during luteinization, probably under LH stimulation, and suggest that integrin alpha5 is involved in CL formation via interaction with its ligand FN.

Antigens, CD↗

PubMed2000

alpha5 integrin distribution and TGFbeta1 gene expression in supraglottic carcinoma: their role in neoplastic local invasion and metastasis.

BACKGROUND: Head and neck carcinomas are characterized by tumor-infiltrating lymphocytes (TIL) producing cytokines. Adhesion molecules, extracellular matrix proteins (ECMPs), and cytokines regulate cell-cell and cell-ECMPs interactions. We investigated the distribution of these proteins to contribute to better understanding of their role in local tumor invasion and metastasis. METHODS: Distribution of integrins, laminin, type IV collagen, tenascin, and fibronectin was immunohistochemically evaluated in 13 supraglottis carcinomas. Cytokines gene expression was assessed by reverse-transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Neoplastic cells were alpha2beta1, alpha3beta1, alpha4beta1, alpha5beta1 and alpha6beta1 positive. Normal and metaplastic epithelium was alpha5beta1 negative; the stroma of primary and metastatic tumors was tenascin and fibronectin positive. TGFbeta1 and IFNgamma gene expression was observed in the majority of tumors. CONCLUSIONS: Because TGFbeta1 is known to down-modulate immune processes and to increase alpha2beta1, alpha5beta1, and tenascin distribution, we propose that their expression in neoplastic cells of supraglottis carcinoma might represent an immune-related process able to help tumor growth and progression.

Antigens, CD↗

PubMed2001

The beta2, alpha4, alpha5 integrins and selectins mediate chemotactic factor and endotoxin-enhanced neutrophil sequestration in the lung.

Intravascular chemotactic factor activation of neutrophils (polymorphonuclear leukocytes; PMNLs), associated with actin polymerization resulting in PMNL stiffening, induces rapid and transient sequestration in the pulmonary vasculature and lung dysfunction. Recent studies have proposed that this sequestration is mediated by physical lodging of PMNLs because of loss of deformability. To examine the contribution of cell adhesion molecules in this process, we used blocking monoclonal antibodies (mAbs) to rat selectins and integrins in a model of PMNL margination (reflected by acute blood neutropenia) induced by N-formyl-met-leu-phe (FMLP) chemotactic factor infusion in normal or lipopolysaccharide (LPS)-primed rats. Blood PMNL levels dropped by 70% within 1 minute and for the duration of FMLP infusion (20 minutes) in normal or by 90% in LPS-primed rats. Pretreatment with mAbs to beta2(WT.3), VLA-4(TA-2 F(ab)(2)), and VLA-5 (HMalpha5 F(ab)(2)) in combination inhibited the decrease by 50% and to a greater degree than beta2 blockade alone (35% inhibition). F(ab)(2) mAbs to L-(HRL-3), P-(RMP-1), plus E-(RME-1) selectins had no effect but they potentiated inhibition by anti-beta2 + anti-VLA-4 + anti-VLA5 mAb treatment (69% inhibition, P < 0.05). Similar results were observed in the first 6 minutes in LPS-primed rats with complete inhibition of sequestration thereafter by combined selectin and integrin blockade. These results indicate that besides PMNL stiffening because of actin polymerization, both selectins and integrins substantially contribute to activated PMNL sequestration in the lung.

Animals↗

PubMed2001

Reduced blood vessel formation and tumor growth in alpha5-integrin-negative teratocarcinomas and embryoid bodies.

Embryonic stem (ES) cells-wild-type, heterozygous, or null for alpha5-integrin-were injected ectopically into syngeneic mice to develop teratocarcinomas. alpha5-null-derived teratocarcinomas were significantly smaller than the wild-type or alpha5 heterozygous tumors. Histological analysis revealed the presence of tissues derived from all three germ layers, in all tumors. However, alpha5-null teratocarcinomas displayed less undifferentiated tissue than did the controls. Decreased proliferation and increased apoptosis were observed in the undifferentiated areas of the alpha5-null teratocarcinomas. The expression of extracellular matrix proteins, fibronectin and tenascin-C, and the basement membrane components, laminin, entactin/nidogen, and collagen IV, was similar in the different tumors, although the deposition of these molecules was more disorganized in alpha5-null teratocarcinomas. The absence of alpha5-integrin in the various tissues of the alpha5-null tumors was confirmed by immunohistochemistry. Many vessels, but not all, stained positively for alpha5-integrin, showing that they were host derived. Analysis of the area occupied by vessels revealed, on average, an 8-fold decrease in alpha5-null teratocarcinomas compared with control tumors. Staining for smooth muscle alpha-actin showed that pericytes and smooth muscle cells were recruited around the vessels in all tumors, suggesting similar vessel differentiation. Deposition of EIIIA and EIIIB and fibronectin around the vessels was observed in all tumors. The fact that some, although few, alpha5-integrin-negative vessels existed in alpha5-null tumors indicated that alpha5-/- ES cells could differentiate into endothelial cells. Endothelial cell differentiation and vessel formation were analyzed also in vitro. alpha5-null ES cells were differentiated into embryoid bodies, although they were delayed in growth and attachment. Differentiation into endothelial cells was achieved, but the organization into a complex vasculature was delayed compared with controls. We conclude that alpha5beta1-integrin plays a significant role in vessel formation both in ES cell cultures and in teratocarcinomas. Reduced vascularization likely contributed to the reduced proliferation and increased apoptosis observed in alpha5-null teratocarcinomas.

Animals↗

PubMed2000

Nischarin, a novel protein that interacts with the integrin alpha5 subunit and inhibits cell migration.

Integrins have been implicated in key cellular functions, including cytoskeletal organization, motility, growth, survival, and control of gene expression. The plethora of integrin alpha and beta subunits suggests that individual integrins have unique biological roles, implying specific molecular connections between integrins and intracellular signaling or regulatory pathways. Here, we have used a yeast two-hybrid screen to identify a novel protein, termed Nischarin, that binds preferentially to the cytoplasmic domain of the integrin alpha5 subunit, inhibits cell motility, and alters actin filament organization. Nischarin is primarily a cytosolic protein, but clearly associates with alpha5beta1, as demonstrated by coimmunoprecipitation. Overexpression of Nischarin markedly reduces alpha5beta1-dependent cell migration in several cell types. Rat embryo fibroblasts transfected with Nischarin constructs have "basket-like" networks of peripheral actin filaments, rather than typical stress fibers. These observations suggest that Nischarin might affect signaling to the cytoskeleton regulated by Rho-family GTPases. In support of this, Nischarin expression reverses the effect of Rac on lamellipodia formation and selectively inhibits Rac-mediated activation of the c-fos promoter. Thus, Nischarin may play a negative role in cell migration by antagonizing the actions of Rac on cytoskeletal organization and cell movement.

3T3 Cells↗

PubMed2002

TGF-beta1-stimulated osteoblasts require intracellular calcium signaling for enhanced alpha5 integrin expression.

The osteoactive factor, transforming growth factor beta1 (TGF-beta1), influences osteoblast activity and bone function. We recently characterized a Smad-independent TGF-beta1-induced Ca(2+) signal in human osteoblasts (HOB) and demonstrated its importance in cell adhesion. Here, we further elucidate the role of the TGF-beta1 Ca(2+) signal in the mechanics of HOB adhesion. Osteoblast interaction with fibronectin (FN) through alpha5beta1 integrin is principally responsible for osteoblast-substrate adhesion. Our results show that the TGF-beta1 intracellular Ca(2+) signal is responsible, in part, for stimulation of alpha5 integrin expression, but not beta1 integrin or FN expression. Increased alpha5 integrin protein and mRNA expression was seen as early as 12 h after TGF-beta1 treatment, but was inhibited by cotreatment with nifedipine, a Ca(2+) channel blocker. TGF-beta1 increased both FN and beta1 integrin protein production within 48 h, independent of nifedipine cotreatment. Immunofluorescence observations revealed that TGF-beta1 increased alpha5 integrin staining, clustering, and colocalization with the actin cytoskeleton, effects that were blocked by nifedipine. The TGF-beta1 Ca(2+) signal, a pathway crucial for HOB adhesion, enhances alpha5 integrin expression, focal contact formation, and cytoskeleton reorganization. These early events are necessary for osteoblast adhesion; thus they determine the fate of the cell and ultimately affect bone function.

Actins↗

PubMed2001

Serum factors regulate the expression of the proliferation-related genes alpha5 integrin and keratin 1, but not keratin 10, in HaCaT keratinocytes.

In the highly coordinated programme of gene expression during keratinocyte proliferation and differentiation, alpha5 integrin and keratins 1 and 10 (K1/K10) may play important regulatory roles. We were interested in seeing whether, in continuously growing, immortalized HaCaT keratinocytes, similar to normal keratinocytes, the expression of alpha5 integrin and K1/K10 was related to cell proliferation and differentiation. After release from cell quiescence the expression of alpha5 integrin, both at the mRNA and protein levels, was upregulated in the cells. At the same time, K1/K10 mRNA and protein expression decreased dramatically, while the mRNA for D1 cyclin became detectable, and the cells became highly proliferative. These findings indicate that alpha5 integrin and K1/K10 are involved in the regulation of HaCaT proliferation and differentiation, as in normal keratinocytes. However, HaCaT cells are different from normal keratinocytes in their ability to lose K1/K10 expression. There is no evidence that the expression of K1/K10 can be reversed in normal keratinocytes. This ability of dedifferentiation might be a unique feature of HaCaT cells and may be a key component of their immortalized nature. We also found that serum factors regulate mRNA expression of alpha5 integrin and K1, but not of K10, in HaCaT cells. This information could be relevant to the understanding of normal epidermal differentiation.

Antigens, CD↗

PubMed2002

TGF-beta1 calcium signaling increases alpha5 integrin expression in osteoblasts.

TGF-beta1 is a potent osteoactive factor and exhibits a wide variety of effects on osteoblasts, most of which are mediated through receptor associated Smad proteins. We have recently reported a novel TGF-beta1 intracellular Ca2+ signaling pathway in osteoblasts, and found that this signaling is required for the TGF-beta1 mediated enhancement of osteoblast adhesion to substrate. Given that interaction between the extracellular matrix protein fibronectin and alpha5beta1 integrin on the cell surface is principally responsible for osteoblast substrate adhesion, we examined here whether the TGF-beta1 stimulated Ca2+ signal is involved in this pathway. Our results show that, in primary human osteoblasts, the TGF-beta1 induced intracellular Ca2+ signal is responsible, in part, for the stimulation of expression of alpha5 integrin, but not of beta1 integrin or fibronectin. Increased levels of alpha5 integrin protein and mRNA were seen as early as 12 h after TGF-beta1 treatment, but were inhibited by co-treatment of cells with nifedipine, a selective L-type Ca2+ channel blocker. TGF-beta1 treatment increased both fibronectin and beta1 integrin protein production within 48 h, in a manner unaffected by co-treatment with nifedipine. Immunofluorescence observations revealed that TGF-beta1 treatment resulted in increased alpha5 integrin staining, and more prominent alpha5 integrin clustering, with increased co-localization with the actin cytoskeleton, effects that were blocked by co-treatment with nifedipine. The TGF-beta1 induced intracellular Ca2+ signal in human osteoblasts is thus an important mechanistic step in the regulation of alpha5 integrin expression, later contributing to enhanced cell adhesion.

Calcium Channel Blockers↗

PubMed1999

Leukocytes utilize both alpha4 and alpha5 integrins for intraislet infiltration in non-obese diabetic mice.

The loss of insulin-producing cells during the development of type 1 diabetes is dependent on leukocyte infiltration of beta-islets in the pancreas. Injection of antibodies to integrins and their ligands has been shown to prevent the development of diabetes in non-obese diabetic (NOD) mice. However, little is known about the progression of infiltration by leukocytes after their homing and extravasation into the pancreas. In the present study, the effect of monoclonal antibodies (mAbs) to alpha4 and alpha5 integrins on leukocytes that had infiltrated the islets was characterized in NOD mice at 10 weeks of age when insulitis was in progress, or in mice with recent onset of diabetes. Injection of mAbs to either alpha4 or alpha5 integrins had little effect on the extent of leukocyte infiltration in 10-week-old or diabetic mice. In contrast, leukocyte infiltration was significantly reduced upon injection of mAbs to both alpha4 and alpha5 integrins. The reduction in leukocyte infiltration was due to decreases in the percentage of islets with intraislet infiltration. However, the observed effect of mAbs to alpha4 and alpha5 integrins was reversible, since intraislet infiltration resumed upon termination of antibody treatment. Results suggest that after homing to the pancreas, leukocytes utilize both alpha4 and alpha5 integrins for intraislet infiltration.

Animals↗

PubMed1998

alpha4 and alpha5 integrins costimulate the CD3-dependent proliferation of fetal thymocytes.

Although integrin receptors have been shown to function as costimulatory molecules on mature thymocytes and T cells, it is not known whether these receptors can function as costimulatory molecules on immature thymocytes. Previous studies have shown that the expression of alpha4 and alpha5 integrins were significantly higher on immature, adult CD4(-)CD8(-) thymocytes than on either mature thymocytes or T cells, suggesting that these receptors are involved in early thymocyte development. In this study, we show that day 16 fetal thymocytes express levels of alpha4 and alpha5 equivalent to those of adult CD4(-)CD8(-) thymocytes. Immobilized fibronectin, a ligand for alpha4 and alpha5 integrins, was found to enhance the CD3-dependent proliferation of these fetal thymocytes. In the presence of IL-7, the magnitude of the proliferative response increased with time of incubation, resulting in a dramatic increase in the percentage of gammadelta thymocytes. The enhancement of proliferation by fibronectin was abrogated by soluble antibodies against alpha4 and alpha5, whereas immobilized mAb to alpha4 and alpha5 substituted for fibronectin in enhancing CD3-dependent proliferation, demonstrating that alpha4 and alpha5 integrins were responsible for the enhanced proliferation by fibronectin. Anti-alpha4 mAb enhanced proliferation of fetal thymocytes by 100%, whereas anti-alpha5 mAb and anti-CD28 mAb enhanced proliferation by 25%. Other costimulatory molecules, such as CD2, FcRgamma, and Thy-1, had no effect on the CD3-dependent proliferation of day 16 fetal thymocytes. This study demonstrates that alpha4 and alpha5 integrins are capable of costimulating fetal thymocytes.

Animals↗

PubMed1999

EC3, a novel heterodimeric disintegrin from Echis carinatus venom, inhibits alpha4 and alpha5 integrins in an RGD-independent manner.

EC3, a heterodimeric disintegrin (Mr = 14,762) isolated from Echis carinatus venom is a potent antagonist of alpha4 integrins. Two subunits called EC3A and EC3B were isolated from reduced and alkylated EC3 by reverse-phase high performance liquid chromatography. Each subunit contained 67 residues, including 10 cysteines, and displayed a high degree of homology to each other and to other disintegrins. EC3 inhibited adhesion of cells expressing alpha4beta1 and alpha4beta7 integrins to natural ligands vascular cell adhesion molecule 1 (VCAM-1) and mucosal addressin cell adhesion molecule 1 (MadCAM-1) with IC50 = 6-30 nM, adhesion of K562 cells (alpha5beta1) to fibronectin with IC50 = 150 nM, and adhesion of alphaIIbbeta3 Chinese hamster ovary cells to fibrinogen with IC50 = 500 nM; it did not inhibit adhesion of alphavbeta3 Chinese hamster ovary cells to vitronectin. Ethylpyridylethylated EC3B inhibited adhesion of Jurkat cells to immobilized VCAM-1 (IC50 = 6 microM), whereas EC3A was inactive in this system. The MLDG motif appeared to be essential for activity of EC3B. Linear MLDG peptide inhibited the adhesion of Jurkat to VCAM-1 in a dose-dependent manner (IC50 = 4 mM), whereas RGDS peptide was not active at the same concentration. MLDG partially inhibited adhesion of K562 cells to fibronectin (5-10 mM) in contrast to RGDS peptide (IC50 = 3 mM), inhibiting completely at 10 mM.

Amino Acid Sequence↗

PubMed2001

Expression of dominant-negative form of Ets-1 suppresses fibronectin-stimulated cell adhesion and migration through down-regulation of integrin alpha5 expression in U251 glioma cell line.

Ets transcription factors are associated with tumor malignancy. We reported previously that the stable transfection of the dominant-negative form of Ets-1 (Ets-DN) in the glioma cell line U251 induced down-regulation of urokinase-type plasminogen activator mRNA expression and invasiveness (M. Nakada et al., J. Neuropathol. Exp. Neurol., 58: 329-334, 1999). Here we analyzed effects of Ets-DN expression on cell adhesion, migration, and phosphorylation of focal adhesion kinase. U251 cells expressing Ets-DN (U251-DN) showed reduced cell adhesion, spreading, and extension of actin stress fibers on dishes coated with fibronectin but not on dishes coated with collagen. Migration of U251-DN cells was found to be significantly inhibited compared with that of parental cells when examined by wound-induced migration assay on fibronectin-coated dishes. Phosphorylation levels of focal adhesion kinase in U251-DN cells were also attenuated on dishes coated with fibronectin. Reduced expression level of integrin alpha5 subunit in U251-DN cells was demonstrated by semiquantitative reverse transcription-PCR analysis. Semiquantitative reverse transcription-PCR of surgical samples of brain tumors revealed that the expression level of Ets-1 mRNA correlated with that of integrin alpha5 mRNA in glioma. The experimental metastatic ability of U251-DN cells examined in chick embryo was considerably lower than that of parental cells. These results suggest that Ets-1 contributes to glioma malignancy by up- regulating expression of the integrin alpha5 subunit, which composes integrin alpha5beta1 and mediates intracellular signaling and the subsequent acceleration of the invasive process, including cell adhesion and migration.

Animals↗

PubMed2001

Immunohistochemical expression of the alpha5 integrin subunit in the normal adult rat central nervous system.

We investigated the distribution of the alpha5 integrin subunit in the normal adult rat CNS using immunohistochemical methods. Results indicated that the alpha5 integrin subunit was expressed on the vast majority of neurons throughout the brain and spinal cord. In general, neurons showed diffuse cytoplasmic labelling, although many cortical neurons in layers 4 and 5 did show punctate labelling on the cell surface. In addition, axons within the white matter of the brainstem and caudal CNS areas were labelled, with the most intense labelling seen within the white matter of the spinal cord. In addition, labelling of astrocytes was seen throughout white matter, with particularly heavy astrocyte labelling in the spinal cord. The widespread distribution of the alpha5 subunit suggests a general function for the alpha5beta1 integrin receptor (the only integrin receptor that includes the alpha5 subunit) in the adult CNS. The increased expression of fibronectin, the only known ligand for the alpha5beta1 integrin receptor, known to occur around the site of a CNS lesion suggests a possible role for the alpha5beta1 receptor in the response of neurons in the vicinity of a CNS injury.

Animals↗

PubMed2000

The alpha2 and alpha5 integrin genes: identification of transcription factors that regulate promoter activity in epidermal keratinocytes.

We analysed the activity of the proximal promoters of the alpha2 and alpha5 integrin genes in human keratinocytes. An AP-1 site, found in the alpha5 but not the alpha2 promoter, bound c-Jun/c-Fos dimers and contributed strongly to promoter activity. Both promoters had a CCAAT/enhancer binding protein (C/EBP) binding site: the alpha5 C/EBP element enhanced activity, while the alpha2 site was a negative regulatory element. C/EBP overexpression repressed the activity of both promoters, but the effect was independent of occupancy of the identified C/EBP binding sites, suggesting interactions with additional transcription factors. We propose that upregulation of C/EBPs contributes to the inhibition of integrin transcription during keratinocyte terminal differentiation, while AP-1 factors play a role in the selective induction of the alpha5 gene during wound healing.

Antigens, CD↗

PubMed1999

Up-regulation of integrin alpha5 by a C-terminus four-amino-acid sequence of substance P (phenylalanine-glycine-leucine-methionine- amide) synergistically with insulin-like growth factor-1 in SV-40 transformed human corneal epithelial cells.

We previously reported that substance P and insulin-like growth factor-1 (IGF-1) synergistically facilitate corneal epithelial migration in vivo and in vitro. We investigated whether the substance P-derived tetrapeptide (phenylalanine-glycine-leucine-methionine-amide, FGLM) can up-regulate the receptors for fibronectin and cellular adhesion to fibronectin matrix in the presence or absence of IGF-1 in cultured SV-40 transformed human corneal epithelial (HCE) cells. The combination of both FGLM and IGF-1 and substance P and IGF-1 significantly increased the number of cells adhered to the fibronectin matrix and the expression of integrin alpha5. The synergistic effect of FGLM and IGF-1 on the adhesion of HCE cells to the fibronectin matrix is partly carried through up-regulation of integrin alpha5 expression in HCE cells. These results showed that the four-amino-acid sequence at the C-terminus of substance P completely mimics the substance P molecule in terms of synergism with IGF-1 on adhesion of epithelial cells to the fibronectin matrix.

Antigens, CD↗