A member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), MICA, has been recently identified near the HLA-B gene on the short arm of human chromosome 6. The predicted amino acid sequence of the MICA chain suggests that it folds similarly to typical class I chains and may have the capacity to bind peptides or other short ligands. Therefore, MICA is predicted to have a specialized function in antigen presentation or T cell recognition. During nucleotide sequence analyses of the MICA genomic clone, we found a triplet repeat microsatellite polymorphism of (GCT͞AGC) n in the transmembrane (TM) region of the MICA gene. In 68 HLA homozygous B cell lines, 5 distinct alleles of this microsatellite sequence were detected. One of them contained an additional one base insertion that created a frameshift mutation resulting in a premature termination codon in the TM region. This particular allele may encode a soluble, secreted form of the MICA molecule. In addition, we have investigated this microsatellite polymorphism in 77 Japanese patients with Behçet disease, which is known to be associated with HLA-B51. The microsatellite allele consisting of 6 repetitions of GCT͞AGC was present at significantly higher frequency in the patient group (Pc ؍ 0.00055) than in a control population. Furthermore, the (GCT͞AGC) 6 allele was present in all B51 positive patients and in an additional 13 B51 negative patients. These results suggest the possibility of a primary association of Behçet disease with MICA rather than HLA-B.
Polarization of sintered hydroxyapatite (HAp) ceramics by application of an external dc field at higher temperature was analyzed by thermally stimulated depolarization current (TSDC) measurements. The mechanisms for the polarization and depolarization of HAp were discussed in relation to the instability of the protons in the hydroxide groups. The TSDC spectra consisted of broad peaks, while the ferroelectric substances such as the BaTiO3 ceramics exhibited a sharp peak. Although the maximum current density of 7.87 nA cm−2 for the HAp polarized at 400 °C under 1.0 kV cm−1 was approximately 1/12 lower than that of BaTiO3, the polarization charge of 14.9 μC cm−2 was almost twice as large as that of BaTiO3. Considering the activation energy of 0.72–0.89 eV for the depolarization, it was revealed that the polarization of HAp was ascribed to the migration of protons in the columnar OH− channels with a micrometer-order distance. It was also found that the polarization charge was large and long enough to enhance the biological reactivity of HAp ceramics for biomedical implants.
Aberrant epithelial-mesenchymal transition (EMT) is involved in development of fibrotic disorders and cancer invasion.Alterations of cell-extracellular matrix interaction also contribute to those pathological conditions. However, the functional interplay between EMT and cell-extracellular matrix interactions remains poorly understood. We now show that the inflammatory mediator tumor necrosis factor-␣ (TNF-␣) induces the formation of fibrotic foci by cultured retinal pigment epithelial cells through activation of transforming growth factor- (TGF-) signaling in a manner dependent on hyaluronan-CD44-moesin interaction. TNF-␣ promoted CD44 expression and moesin phosphorylation by protein kinase C, leading to the pericellular interaction of hyaluronan and CD44. Formation of the hyaluronan-CD44-moesin complex resulted in both cell-cell dissociation and increased cellular motility through actin remodeling. Furthermore, this complex was found to be associated with TGF- receptor II and clathrin at actin microdomains, leading to activation of TGF- signaling. We established an in vivo model of TNF-␣-induced fibrosis in the mouse eye, and such ocular fibrosis was attenuated in CD44-null mice. The production of hyaluronan and its interaction with CD44, thus, play an essential role in TNF-␣-induced EMT and are potential therapeutic targets in fibrotic disorders. The epithelial-mesenchymal transition (EMT)2 of epithelial cells is characterized by the loss of epithelial characteristics and the gain of mesenchymal attributes. During this transition, epithelial cells down-regulate cell-cell adhesion systems, lose their polarity, and acquire a mesenchymal phenotype associated with increased interaction with the extracellular matrix (ECM) and enhanced migratory capacity. The EMT is considered a critical event in metazoan embryogenesis as well as in physiological processes such as wound healing. However, it also plays an important role in pathological settings such as fibrotic disorders in various organs as well as cancer invasion and metastasis.The EMT associated with physiological processes is triggered by members of the transforming growth factor- (TGF-) family of proteins that function as morphogens (1). In vitro studies have also shown that TGF- is the major inducer of the EMT in epithelial cells (2). Fibrotic disorders associated with pathological EMT result from a series of events including inflammation, leukocyte infiltration, and the production of cytokines and growth factors. TGF- is one of the cytokines produced during inflammation and is, therefore, thought to heavily contribute to EMT-associated fibrosis (3). However, given that TGF- also possesses anti-inflammatory properties, the mechanism of pathological EMT induced by the inflammatory response may be multifactorial and differ from that of physiological EMT.In addition to growth factors, changes in the ECM microenvironment contribute to the EMT. Epithelial cells cultured in a type I collagen gel were found to undergo the EMT (4). Furthermore, collagen-induce...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.