Osteopontin (OPN) contains at least two major integrin recognition domains, Arg159-Gly-Asp161 (RGD) and Ser162-Val-Val-Tyr-Gly-Leu-Arg168 (SVVYGLR), recognized by alphavbeta3 and alpha5beta1 and alpha4 and alpha9 integrins, respectively. OPN is specifically cleaved by thrombin and matrix metalloproteinase (MMP)-3 or MMP-7 at a position of Arg168/Ser169 (R/S) and Gly166/Leu167 (G/L), respectively. We in this study examined the requirement of residues within SVVYGLR for the alpha4 and alpha9 integrin recognition and how MMP-cleavage influences the integrin recognition. The residues, Val164, Tyr165, and Leu167 are critical for alpha4 and alpha9 integrin recognition in both cell adhesion and cell migration. The residue Arg168 is additionally required for alpha9 integrin recognition in cell adhesion and this explains why alpha9 integrin binds to only thrombin cleaved form of OPN. alpha4 integrin is able to bind to SVVYG (MMP-cleaved form of RAA OPN-N half), while alpha9 integrin is not, supporting the above notion that Arg168 is additionally required for alpha9 integrin-mediated cell adhesion. The residue Val163 is important for alpha4, but not for alpha9 integrin recognition in cell migration. Importantly, we found that the replacement of Arg168 by Ala (R168A mutant) induces the augmentation of cell migration via alpha4 and alpha9 integrins.
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http://dx.doi.org/10.1016/j.matbio.2008.10.002 | DOI Listing |
Biosci Biotechnol Biochem
November 2024
Department of Molecular Immunology, Faculty of Pharmaceutical Sciences, Fukuyama University, Gakuen-cho 1, Fukuyama, Hiroshima 729-0292, Japan.
Carnosic acid is a naturally occurring, plant-derived polyphenolic abietane diterpene with anti-tumor properties. However, its underlying mechanisms are still unclear. Therefore, we investigated the effects of carnosic acid on lung metastasis in a murine melanoma model.
View Article and Find Full Text PDFSci Adv
April 2024
Center for Autoimmune Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Acetylcholine is produced in the spleen in response to vagus nerve activation; however, the effects on antibody production have been largely unexplored. Here, we use a chronic vagus nerve stimulation (VNS) mouse model to study the effect of VNS on T-dependent B cell responses. We observed lower titers of high-affinity IgG and fewer antigen-specific germinal center (GC) B cells.
View Article and Find Full Text PDFZoolog Sci
October 2022
Faculty of Health Science, Kumamoto Health Science University, Kita-ku, Kumamoto 861-5598, Japan,
CD34 is expressed in various cell types in various tissues/organs, and has been regarded as being expressed in progenitors in various differentiation pathways. On the other hand, morphological studies have reported the presence of a special type of interstitial cells, telocytes, which generally express CD34, and have extremely long moniliform prolongations in various tissues/organs in vertebrates. We have recently reported the successful reconstruction of testicular structures by 3-D re-aggregation culture of dissociated prepubertal mouse testicular cells, and the roles of CD34 cells in the reconstruction.
View Article and Find Full Text PDFMatrix Biol
August 2022
Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
Alterations in extracellular matrix (ECM) components that modulate inflammatory cell behavior have been shown to serve as early starters for multifactorial diseases such as fibrosis and cancer. Here, we demonstrated that loss of the ECM glycoprotein EMILIN-1 alters the inflammatory context in skin during IMQ-induced psoriasis, a disease characterized by a prominent inflammatory infiltrate and alteration of vessels that appear dilated and tortuous. Abrogation of EMILIN-1 expression or expression of the EMILIN-1 mutant E933A impairs macrophage polarization and leads to imbalanced tissue homeostasis.
View Article and Find Full Text PDFJ Thromb Haemost
May 2022
Division of Hematology, Stanford University School of Medicine, Stanford, California, USA.
Background: Osteopontin (OPN) is a multifunctional proinflammatory matricellular protein overexpressed in multiple human cancers and associated with tumor progression and metastases. Thrombin cleavage of OPN reveals a cryptic binding site for α β and α β integrins.
Methods: Thrombin cleavage-resistant OPN knock-in (OPN-KI) mice were generated and compared to OPN deficient mice (OPN-KO) and wild type (WT) mice in their ability to support growth of melanoma cells.
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