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Hierarchical Quatsome-RGD Nanoarchitectonic Surfaces for Enhanced Integrin-Mediated Cell Adhesion.

The synthesis and study of the tripeptide Arg-Gly-Asp (RGD), the binding site of different extracellular matrix proteins, e.g., fibronectin and vitronectin, has allowed the production of a wide range of cell adhesive surfaces. Although the surface density and spacing of the RGD peptide at the nanoscale have already shown a significant influence on cell adhesion, the impact of its hierarchical nanostructure is still rather unexplored. Accordingly, a versatile colloidal system named quatsomes, based on fluid nanovesicles formed by the self-assembling of cholesterol and surfactant molecules, has

Integrin α7 Mutations Are Associated With Adult-Onset Cardiac Dysfunction in Humans and Mice.

Background Integrin α7β1 is a major laminin receptor in skeletal and cardiac muscle. In skeletal muscle, integrin α7β1 plays an important role during muscle development and has been described as an important modifier of skeletal muscle diseases. The integrin α7β1 is also highly expressed in the heart, but its precise role in cardiac function is unknown. Mutations in the integrin α7 gene (ITGA7) have been reported in children with congenital myopathy. Methods and Results In this study, we described skeletal and cardiac muscle pathology in Itga7-/- mice and 5 patients from 2 unrelated families w

The First Snake Venom KTS/Disintegrins-Integrin Interactions Using Bioinformatics Approaches.

Snake venom contains a number of active molecules that have been shown to possess high anti-tumor activities; disintegrins are an excellent example among these. Their ability to interact and bind with integrins suggests that they could be very valuable molecules for the development of new cancer therapeutic approaches. However, in the absence of a clear Lysine-Threonine-Serine (KTS) Disintegrins Integrin interaction model, the exact compound features behind it are still unknown. In this study, we investigated the structural characteristics of three KTS-disintegrins and the interaction mechanis…

Defective Leukocyte β2 Integrin Expression and Reactive Oxygen Species Production in Neonates.

Neonates are highly susceptible to bacterial infections, which represent a major source of mortality and morbidity in this age category. It is recognized that β2 integrins play a critical role in innate immunity by mediating leukocyte vascular adhesion, transmigration and bacterial phagocytosis. Therefore, we aimed to assess if the impaired immune functions seen in newborns may derive, in part, from a transient insufficient β2 integrin expression. In the present study we measured baseline lymphocyte function-associated antigen-1 (LFA-1 or CD11a/CD18), macrophage-1 antigen (MAC-1 or CD11b/CD18)…

Targeting integrin αvβ3 by a rationally designed protein for chronic liver disease treatment.

Chronic Liver Diseases (CLD) are characterized by abnormal accumulation of collagen fibrils, neo-angiogenesis, and sinusoidal remodeling. Collagen deposition along with intrahepatic angiogenesis and sinusoidal remodeling alters sinusoid structure resulting in portal hypertension, liver failure, and other complications. Efforts were made to develop treatments for CLDs. However, the success of such treatments is limited and unpredictable. We report a strategy for CLD treatment by induction of integrin αvβ3 mediated cell apoptosis using a rationally designed protein (ProAgio). ProAgio is designed

Optimized serum stability and specificity of an αvβ6 integrin-binding peptide for tumor targeting.

The integrin αvβ6 is an antigen expressed at low levels in healthy tissue but upregulated during tumorigenesis, which makes it a promising target for cancer imaging and therapy. A20FMDV2 is a 20-mer peptide derived from the foot-and-mouth disease virus that exhibits nanomolar and selective affinity for αvβ6 versus other integrins. Despite this selectivity, A20FMDV2 has had limited success in imaging and treating αvβ6+ tumors in vivo because of its poor serum stability. Here, we explore the cyclization and modification of the A20FMDV2 peptide to improve its serum stability without sacrificing i…

The Amot/integrin protein complex transmits mechanical forces required for vascular expansion.

Vascular development is a complex multistep process involving the coordination of cellular functions such as migration, proliferation, and differentiation. How mechanical forces generated by cells and transmission of these physical forces control vascular development is poorly understood. Using an endothelial-specific genetic model in mice, we show that deletion of the scaffold protein Angiomotin (Amot) inhibits migration and expansion of the physiological and pathological vascular network. We further show that Amot is required for tip cell migration and the extension of cellular filopodia. Ex

Inhibition Effect of Chloroquine and Integrin-Linked Kinase Knockdown on Translation in Melanoma Cells.

The twofold role of autophagy in cancer is often the therapeutic target. Numerous regulatory pathways are shared between autophagy and other molecular processes needed in tumorigenesis, such as translation or survival signaling. Thus, we have assumed that ILK knockdown should promote autophagy, and used together with chloroquine, an autophagy inhibitor, it could generate a better anticancer effect by dysregulation of common signaling pathways. Expression at the protein level was analyzed using Western Blot; siRNA transfection was done for ILK. Analysis of cell signaling pathways was monitored

CYRI-A limits invasive migration through macropinosome formation and integrin uptake regulation.

The Scar/WAVE complex drives actin nucleation during cell migration. Interestingly, the same complex is important in forming membrane ruffles during macropinocytosis, a process mediating nutrient uptake and membrane receptor trafficking. Mammalian CYRI-B is a recently described negative regulator of the Scar/WAVE complex by RAC1 sequestration, but its other paralogue, CYRI-A, has not been characterized. Here, we implicate CYRI-A as a key regulator of macropinosome formation and integrin internalization. We find that CYRI-A is transiently recruited to nascent macropinosomes, dependent on PI3K a

Chlorpyrifos effects on integrin alpha v and beta 3 in implantation window phase.

Chlorpyrifos (CPF), as a worldwide pesticide, can effect on the integrins αv and β3 which play a main role in the implantation window. Therefore, the aim of this study was to consider CPF effects on integrin alpha v and beta 3 in implantation window phase. Thirty female NMRI mice were separated into groups of CPF, sham, and control. After 6 weeks, each group was mated, and on the 5th day of gestation, all mice were euthanized. Estradiol and progesterone levels were detected by the enzyme-linked immunosorbent assay (ELISA) test; two subunits of integrins (αv and β3) genes and proteins of endome…

TDCPP mimics thyroid hormones associated with the activation of integrin αvβ3 and ERK1/2.

Tri(1,3-dichloropropyl) phosphate (TDCPP) potentially damages the thyroid system in humans and animals. However, knowledge of its toxic effects and underlying mechanisms is limited. The present study was conducted to determine the thyroid hormone-disrupting effects of TDCPP and its major metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP) in rat pituitary cell lines (GH3). TDCPP and BDCPP, that mimic the thyroid hormone (TH), promoted GH3 cell proliferation and modulated the progression of the cell cycle at 20 and 200 μmol/L, respectively. Similar to T3, TDCPP and BDCPP also significantly

Laminin and Integrin in LAMA2-Related Congenital Muscular Dystrophy: From Disease to Therapeutics.

Laminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a devastating neuromuscular disease caused by mutations in the LAMA2 gene. These mutations result in the complete absence or truncated expression of the laminin-α2 chain. The α2-chain is a major component of the laminin-211 and laminin-221 isoforms, the predominant laminin isoforms in healthy adult skeletal muscle. Mutations in this chain result in progressive skeletal muscle degeneration as early as neonatally. Laminin-211/221 is a ligand for muscle cell receptors integrin-α7β1 and α-dystroglycan. LAMA2 mutations are correlated w

Integrin-α9 and Its Corresponding Ligands Play Regulatory Roles in Chronic Periodontitis.

Integrin-α9 (ITGA9) and its corresponding ligands are involved in inflammatory and immune responses. The present study aimed to investigate whether ITGA9 participates in the development of chronic periodontitis (ChP) and to explore the underlying mechanisms. We collected gingival tissue and gingival crevicular fluid in vivo from patients to determine the levels of ITGA9 and its ligands. We cultured primary periodontal ligament cells (PDLCs) in vitro and applied small interfering RNA to knock down ITGA9 in order to analyze the changes of inflammatory cytokines and explore the related cellular s

Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation.

Hormones and their receptors play an important role in the development and progression of breast cancer. Hormones regulate the proliferation of breast cancer cells through binding between estrogen or progestins and steroid receptors that may reside in the cytoplasm or be transcriptionally activated as steroid-protein nuclear receptor complexes. However, receptors for nonpeptide hormones also exist in the plasma membrane. Via those receptors, hormones are able to stimulate breast cancer cell proliferation when activated. Integrins are heterodimeric structural proteins of the plasma membrane. Th…

Aberrantly glycosylated integrin α3β1 is a unique urinary biomarker for the diagnosis of bladder cancer.

Bladder cancer (BC) is the most common malignancy of the urinary tract. We developed a new and ELISA kit for detecting aberrantly glycosylated integrin α3β1 (AG31) in human urine. We analysed urine samples (n=408) of patients with BC, renal cell carcinoma (RCC), prostate cancer (PC), cystitis, nephritis, and prostatitis from two centres in China. The subjects in the validation groups (n=2317) were recruited from other centres in China between July 2012 and September 2013. Receiver operating characteristic (ROC) curves were used to determine diagnostic accuracy. AG31 levels in urine samples wer

Role of LFA-1 integrin in the control of a lymphocytic choriomeningitis virus (LCMV) infection.

Leukocyte function-associated antigen 1 (LFA-1) is the most widely expressed member of the β2 integrin family of cell-cell adhesion molecules. Although LFA-1 is thought to regulate multiple aspects of T cell immunity, its role in the response of CD8+ T cells to viral infections remains unclear. Indeed, compelling clinical evidence shows that loss of LFA-1 function predisposes to infection in humans but animal models show limited to no susceptibility to infection. Here, we addressed this conundrum in a mouse model of infection with lymphocytic choriomeningitis virus (LCMV), where CD8+ T cells a

Nasal vaccination of β7 integrin-deficient mice retains elevated IgA immunity.

Understanding the migration of lymphocytes to nonintestinal mucosal sites is fundamental to developing mucosal vaccination strategies. Studi … expression and cell-sorting experiments revealed that β7-/- mice have increased usage of β1 and αE integrins by upper respiratory tract B cells, suggesting that alternative integrins can facilitate lymphocyte migration to the upper respiratory tract, especially in the absence of β7.

Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity.

Immunological memory ensures life-long protection against previously encountered pathogens, and in mice and humans the spleen is an important reservoir for long-lived memory B cells (MBCs). It is well-established that integrins play several crucial roles in lymphocyte survival and trafficking, but their involvement in the retention of MBCs in secondary lymphoid organs, and differences between B cell subsets in their adhesion capacity to ICAM-1 and/or VCAM-1 have not yet been confirmed. Here, we use an autoimmune mouse model, where MBCs are abundant, to show that the highest levels of LFA-1 and…

Effect of integrin AV and B8 gene polymorphisms in patients with traumatic brain injury.

Background: Α few genetic variants are associated with the outcome after traumatic brain injury (TBI). Integrins are glycoprotein receptors that play an important role in the integrity of microvasculature of the brain. Objective: To examine the role of integrin-AV (ITGAV) and integrin-B8 (ITGB8) tag single nucleotide polymorphisms (SNPs) on the outcome of patients with TBI. Methods: 363 participants were included and genotyped for 11 SNPs for ITGAV and 11 for ITGB8 gene. SNPs were tested for associations with the 6-month outcome after TBI, the presence of a hemorrhagic event after TBI, and the…

Diagnostic and prognostic values of integrin α subfamily mRNA expression in colon adenocarcinoma.

The integrin α (ITGA) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in colon adenocarcinoma (COAD) remain elusive. The present study investigated the significance of the expression of ITGA genes in COAD from the perspective of diagnosis and prognosis. A COAD RNA‑sequencing dataset was obtained from The Cancer Genome Atlas. The present study investigated the biological function of the ITGA subfamily genes through bioinformatics analysis. Reverse transcription‑quantitative polymerase chain reaction was applied to

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… Integrins belong to heterodimeric surface receptors, which are composed of non-covalently associated α and β subunits, and as far as we know, the integrin family consists of 18α and 8β members ( 7 – 11 ). … The integrins are the main receptors for extracellular matrix proteins like collagen, fibronectin and laminin. In addition, integrins play a fundamental role in various biological processes via cellular adhesion mechanisms ( 10 , 46 ). …