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αvβ3 integrin

Kwi Hye Koh, Yanxia Cao, Steve Mangos, Nicholas J Tardi, Ranadheer R Dande, Ha Won Lee, Beata Samelko, Mehmet M Altintas, Vincent P Schmitz, Hyun Lee, Kamalika Mukherjee, Vasil Peev, David J Cimbaluk, Jochen Reiser, Eunsil Hahm
Soluble urokinase receptor (suPAR) is a circulatory molecule that activates αvβ3 integrin on podocytes, causes foot process effacement, and contributes to proteinuric kidney disease. While active integrin can be targeted by antibodies and small molecules, endogenous inhibitors haven't been discovered yet. Here we report a novel, renoprotective role for inducible costimulator (ICOS) ligand (ICOSL) in early kidney disease through its selective binding to podocyte αvβ3 integrin. Contrary to ICOSL's immune-regulatory role, ICOSL in non-hematopoietic cells limited the activation of αvβ3 integrin...
February 12, 2019: Journal of Clinical Investigation
Lei Jiang, Hong Zhu, Yi Li, Xiaodong Wu, Huoqiang Wang, Zhen Cheng
Integrin αvβ3 has been considered as a promising biomarker for vulnerable atherosclerotic plaques, and it is highly expressed by those instability associated factors such as macrophages, vessel endothelial cells and smooth muscle cells. Our previous study successfully showed that 64Cu-labeled divalent (containing two RGD motifs) cystine knot peptide, 64Cu-NOTA-3-4A, had high binding affinity and specificity in targeting vulnerable carotid atherosclerotic plaques with increased αvβ3 levels. Therefore, considering that 68Ga has excellent nuclear physical properties for positron emission tomography (PET), this study aimed to investigate the feasibility of using 68Ga-NOTA-3-4A for PET study of vulnerable atherosclerotic plaques...
February 11, 2019: Molecular Pharmaceutics
Carolina V Uliana, Tássia R de Oliveira, Márcia R Cominetti, Ronaldo C Faria
The evaluation of interaction between small molecules and protein is an important step in the discovery of new drugs and to study complex biological systems. In this work, an alternative method was presented to evaluate small-molecule-protein interaction by using ligand capture by protein-coated magnetic particles (MPs) and disposable electrochemical cells. The interaction study was conducted using [10]-gingerol from ginger rhizome and a transmembrane protein αVβ3 integrin. Initially, the electrochemical behavior of the natural compound [10]-gingerol was evaluated with the disposable carbon-based electrodes and presented an irreversible oxidation process controlled by diffusion...
February 9, 2019: Analytical and Bioanalytical Chemistry
R Fraioli, S Neubauer, F Rechenmacher, B M Bosch, K Dashnyam, J-H Kim, R A Perez, H-W Kim, F J Gil, M P Ginebra, J M Manero, H Kessler, C Mas-Moruno
In this communication we report that anchoring αvβ3 or α5β1 integrin-selective RGD peptidomimetics to titanium efficiently tunes mesenchymal stem cell response in vitro and bone growth in rat calvarial defects. Our results demonstrate that this molecular chemistry-derived approach could be successful to engineer instructive coatings for orthopedic applications.
February 8, 2019: Biomaterials Science
Kai Shi, Sheng-Lin Wang, Bin Shen, Feng-Qiang Yu, Dan-Feng Weng, Jian-Hua Lin
BACKGROUND: Osteosarcoma is a malignant bone tumor with a high potential for lung metastasis, and the prognosis for patients with metastatic disease is very poor. The interaction between fibronectin (FN) and integrin αvβ3 in soft-tissue sarcoma promotes cell migration, invasion, and lung metastasis. This study aimed to investigate the prognostic significance of FN and αvβ3 in osteosarcoma. METHODS: Immunohistochemistry and western blotting were used to detect the expression of FN and αvβ3 in 60 osteosarcoma specimens and in 30 osteochondroma specimens...
January 28, 2019: World Journal of Surgical Oncology
Ki-Hye Jung, Yong Jin Lee, Jung Young Kim, Kyo Chul Lee, Ji-Ae Park, Jae Yong Choi
The αvβ3 integrin is a heterodimeric adhesion molecule involved in tumor cell migration and angiogenesis. The integrin is overexpressed in angiogenic tumor endothelial cells, where it typically has a low concentration. This specific expression of αvβ3 makes it a valid biomarker for antiangiogenic and imaging drugs. As a functional imaging modality, positron emission tomography (PET) provides information about biochemical and physiological changes in vivo, due to its unique high sensitivity at the nanomolar scale...
January 7, 2019: Journal of Visualized Experiments: JoVE
Giselle C Yeo, Anthony S Weiss
We challenge the conventional designation of structural matrix proteins primarily as supporting scaffolds for resident cells. The extracellular matrix protein tropoelastin is classically regarded as a structural component that confers mechanical strength and resilience to tissues subject to repetitive elastic deformation. Here we describe how tropoelastin inherently induces a range of biological responses, even in cells not typically associated with elastic tissues and in a manner unexpected of typical substrate-dependent matrix proteins...
January 18, 2019: Proceedings of the National Academy of Sciences of the United States of America
John T Leith, Shaker A Mousa, Aleck Hercbergs, Hung-Yun Lin, Paul J Davis
Radioresistance is a substantial barrier to success in cancer management. A number of molecular mechanisms support radioresistance. We have shown experimentally that the thyroid hormone analogue receptor on the extracellular domain of integrin αvβ3 may modulate the state of radiosensitivity of tumor cells. Specifically, tetraiodothyroacetic acid (tetrac), a derivative of L-thyroxine (T4 ), can reduce radioresistance in cancer cells. In this review, we list a number of intrinsic signal transduction molecules and other host factors that have been reported to support/induce radioresistance in cancer cells and that are also subject to control by T4 through actions primarily initiated at integrin αvβ3...
December 11, 2018: Oncotarget
Han Wen, Wenwu Xiao, Sangita Biswas, Zhaoqing Cong, Xin-Min Liu, Kit S Lam, Yong-Hong Liao, Wenbin Deng
In this study, we established a long-term three-dimensional (3D) culture system by using integrin ligand modified alginate hydrogels to encapsulate and differentiate neural progenitor cells (NPCs) towards oligodendrocyte (OL) lineage cells. The porosity of the hydrogel was optimized by varying the alginate concentrations and then characterized by scanning electronic microscopy (SEM). The Surface Plasmon Resonance (SPR) test was used to confirm the ligand-integrin interactions indicating adherence between the NPC surfaces and the hydrogels...
January 15, 2019: ACS Applied Materials & Interfaces
Kentaro Hozumi, Yui Teranishi, Sayaka Enomoto, Fumihiko Katagiri, Yamato Kikkawa, Motoyoshi Nomizu
Extracellular matrix molecules are recognized by several integrin subtypes, making identification of cross-talk among different integrin subtypes difficult. Here, we evaluated the cross-talk of integrin subtypes using four different integrin-binding peptides (FIB1; integrin αvβ3/α5β1, A2G10; integrin α6β1, EF1zz; integrin α2β1, or 531; integrin α3β1) derived from extracellular matrix molecules. Various combinations of two different integrin-binding peptides were mixed and conjugated on a chitosan matrix at various molar ratios and were evaluated for cell attachment activity...
January 12, 2019: Journal of Biomaterials Applications
Lakshmi Pallavi Ganipineni, Bernard Ucakar, Nicolas Joudiou, Raphaël Riva, Christine Jérôme, Bernard Gallez, Fabienne Danhier, Véronique Préat
We hypothesized that the active targeting of αvβ3 integrin overexpressed in neoangiogenic blood vessels and glioblastoma (GBM) cells combined with magnetic targeting of paclitaxel- and SPIO-loaded PLGA-based nanoparticles could improve accumulation of nanoparticles in the tumor and therefore improve the treatment of GBM. METHODS: PTX/SPIO PLGA nanoparticles with or without RGD-grafting were characterized. Their in vitro cellular uptake and cytotoxicity was evaluated by fluorospectroscopy and MTT assay...
January 11, 2019: Journal of Drug Targeting
L Zhang, A Gülses, N Purcz, J Weimer, J Wiltfang, Y Açil
BACKGROUND: Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors, cilengitide is suggested to be one of the most promising inhibitors. However, little is known about the cellular processes induced during cilengitide chemotherapy in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: For the current study, 3 HNSCC cell lines, SCC4, SCC15 and SCC25; and 3 primary culture cells, TU53, TU57, and TU63 were used...
January 10, 2019: Clinical & Translational Oncology
Filippo Cipriani, Dominik Bernhagen, Carmen Garcia-Arévalo, Israel González de Torre, Peter Timmerman, Jose Carlos Rodriguez-Cabello
Biomaterial design in tissue engineering aims to identify appropriate cellular microenvironments in which cells can grow and guide new tissue formation. Despite the large diversity of synthetic polymers available for regenerative medicine, most of them fail to fully match the functional properties of their native counterparts. In contrast, the few biological alternatives employed as biomaterials lack the versatility that chemical synthesis can offer. Herein, we studied the HUVEC adhesion and proliferation properties of elastin-like recombinamers (ELRs) that were covalently functionalized with each three high-affinity and selectivity αvβ3- and α5β1-binding bicyclic RGD peptides...
January 10, 2019: Biomedical Materials
Chenggang Li, Li Zhou, Yong Xie, Chuang Guan, Haifeng Gao
To investigate the influence of irisin on endometrial receptivity of rats with polycystic ovarian syndrome (PCOS). PCOS rats were randomly divided into PCOS group and irisin group, and normal rats were used as control group. The PCOS group and control group were injected intraperitoneally with normal saline while the irisin group with recombinant irisin. The serum and uterus were obtained. Detect serum sex hormones, including Testosterone (T), Estradiol (E2 ), Progesterone (P), and glucose, insulin levels. Observe endometrial morphology by hematoxylin-eosin staining...
January 9, 2019: Gynecological Endocrinology
Dominik Bernhagen, Vanessa Jungbluth, Nestor Gisbert Quilis, Jakub Dostalek, Paul B White, Kees Jalink, Peter Timmerman
We describe the identification of bicyclic RGD-peptides with high affinity and selectivity for integrin αvβ3 via high-throughput screening of partly randomized libraries. Peptide libraries (~700 different compounds) comprising the universal integrin-binding sequence Arg-Gly-Asp (RGD) in the first loop and a randomized sequence XXX (X being one of 18 canoni-cal L-amino acids) in the second loop, both enclosed by either an L- or D-Cys residue, were converted to bicyclic peptides via reaction with 1,3,5-tris(bromomethyl)benzene (T3)...
January 9, 2019: ACS Combinatorial Science
Sohameh Mohebbi, Tahereh Tohidi Moghadam, Maryam Nikkhah, Mehrdad Behmanesh
Gold nanorods (GNRs) have been nominated as a promising candidate for a variety of biological applications; however, the cationic surfactant layer that surrounds a nanostructure places limits on its biological applicability. Herein, CTAB-GNRs were functionalized via a ligand exchange method using a (C(HK)4-mini PEG-RGD)-peptide to target the overexpressed αvβ3 integrin in cancerous cells, increase the biocompatibility, and gain the ability of gene/drug delivery, simultaneously. To confirm an acceptable functionalization, UV-Visible, FTIR, and Raman spectroscopy, zeta potential, and transmission electron microscopy of nanostructures were done...
January 8, 2019: Nanoscale Research Letters
Joseph Lau, Orit Jacobson, Gang Niu, Kuo-Shyan Lin, François Bénard, Xiaoyuan Chen
Radioligand therapy (RLT) relies on the use of pharmacophores to selectively deliver ionization energy to cancers to exert its tumoricidal effects. Cancer cells that are not directly targeted by a radioconjugate remain susceptible to RLT because of the crossfire effect. This is significant given the inter- and intra-heterogeneity of tumors. In recent years, reversible albumin binders have been used as simple 'add-ons' for radiopharmaceuticals to modify pharmacokinetics and to enhance therapeutic efficacy. In this review, we discuss recent advances in albumin binder platforms used in RLT, with an emphasis on 4-(p-iodophenyl)butyric acid and Evans blue derivatives...
January 8, 2019: Bioconjugate Chemistry
Allison Post, Sevinj Isgandarova, Margarita Martinez-Moczygemba, Mariah Hahn, Brooke Russell, Magnus Hook, Elizabeth Cosgriff-Hernandez
Despite advances in the development of materials for cardiovascular devices, current strategies generally lack the thromboresistance of the native endothelium both in terms of efficacy and longevity. To harness this innate hemostatic regulation and improve long-term hemocompatibility, biohybrid devices are designed to promote endothelialization. Much of the research effort to date has focused on the use of extracellular matrix (ECM)-mimics and coatings to promote endothelial cell adhesion and migration with less attention given to the effect of the supported ECM binding events on hemostatic regulation...
January 3, 2019: Annals of Biomedical Engineering
Haifeng Song, Tao Liu, Wenting Wang, Hailin Pang, Zhe Zhou, Yajie Lv, Tianyu Cao, Da Zhai, Bintao Ma, Huizhong Zhang, Yanguo Zhang
AIMS: Keloids are a dermal fibrotic disease whose etiology remains totally unknown and for which there is no successful treatment. Mechanical tension, in addition, is closely associated with the germination and development of keloids. In this study, we investigated the influence of human keloid-derived mesenchymal stem cells (KD-MSCs) on cell proliferation, collagen synthesis, and expressions of integrin αvβ3 under tension. MAIN METHODS: KD-MSCs and human normal skin-derived mesenchymal stem cells (NS-MSCs) were isolated and cultured in stem cell medium with a gradual increase in the serum concentration...
December 28, 2018: Life Sciences
Ruchi Kakar-Bhanot, Krupanshi Brahmbhatt, Bhagyashree Chauhan, R R Katkam, T Bashir, H Gawde, N Mayadeo, U K Chaudhari, Geetanjali Sachdeva
STUDY QUESTION: Is Rab11a GTPase, a regulator of intracellular trafficking, of significance in endometrial functions? SUMMARY ANSWER: Rab11a is an important component of the cascades involved in equipping the endometrial epithelium (EE) with 'adhesiveness' and 'cohesiveness'. WHAT IS KNOWN ALREADY: Cell adhesion molecules (CAMs) have been investigated extensively for modulation in their endometrial expression during the peri-implantation phase...
December 31, 2018: Human Reproduction
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