Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental autoimmune myocarditis (EAM) is characterized by the appearance of multinucleated giant cells. EAM leads to severe myocardial damage and is a useful model of human giant cell myocarditis. We investigated whether mycophenolate mofetil (MMF), which is a potent immunosuppressant, prevents the development of myocarditis in a rat EAM model, and focused on the role of osteopontin (OPN) in the pathogenesis of this disorder. Adult Lewis rats were immunized with porcine cardiac myosin to establish EAM. The early MMF treatment completely prevented the development of EAM, and the late MMF treatment was also effective even against established EAM. Echocardiogram demonstrated that left ventricular function was also improved by the treatment with MMF. Real-time RT-PCR analysis showed that both early and late MMF treatments significantly inhibited myocarditis-induced OPN mRNA expression in the heart. Immunohistochemistry revealed that OPN expression was prominent in the myocardium on day 14, whereas expression was observed in the infiltrated macrophages on day 21. Mycophenolic acid (MPA) did inhibit agonist-induced OPN expression in cultured cardiomyocytes. These results show the therapeutic potential of MMF for autoimmune myocarditis and provide new insights into the pathogenesis of this disease.
J Mol Cell Cardiol 2005 Sep
PMID:Mycophenolate mofetil prevents the development of experimental autoimmune myocarditis. 1597 15

The paranasal sinuses remain elusive both in terms of function and in the proximate mechanism of their development. The present study sought to describe the maxillary sinuses (MSs) in three species of callitrichid primates at birth, a time when secondary pneumatization occurs rapidly in humans. The MSs were examined in serially sectioned and stained slides from the heads of two Callithrix jacchus, one Leontopithecus rosalia, and two Saguinus geoffroyi. Specimens were examined microscopically regarding the distribution of osteoclasts and osteoblasts along the osseous boundaries of the MS and other parts of the maxillary bone. Selected sections were immunohistochemically evaluated for the distribution of osteopontin (OPN), which facilitates osteoclast binding. Taken together, OPN immunoreactivity and bone cell distribution suggested trends of bone resorption/deposition that were consistent among species for the superior (roof) and inferior (floor) boundaries of the MS. Expansion at the roof and floor of the MS appeared to correspond to overall vertical midfacial growth in callitrichids. Much more variability was noted for the lateral (alveolar) and medial (nasal walls) of the MS. Unlike the other species, the nasal wall of Saguinus was static and mostly composed of inferior portions of the nasal capsule that were undergoing endochondral ossification. The variation seen in the alveolar walls may relate to the presence or absence of adjacent structures, although it was noted that adjacency of deciduous molars influenced medial drift of the alveolar wall in Saguinus but not Leontopithecus. The results of this study are largely consistent with the "structural" or "architectural" hypothesis of sinus formation with respect to vertical MS enlargement, and the variable cellular/OPN distribution found along the nasal and alveolar walls was evocative of Witmer's (J Vert Paleontol 1997;17:1-73) epithelial hypothesis in revealing that most expansion occurred in regions unopposed by adjacent structures.
Anat Rec A Discov Mol Cell Evol Biol 2005 Aug
PMID:Secondary pneumatization of the maxillary sinus in callitrichid primates: insights from immunohistochemistry and bone cell distribution. 1598 87

Early T lymphocyte activator 1 (Eta-1), also known as Osteopontin, is a cytokine produced by macrophages and T lymphocytes. It is involved in the regulation of IL-12 and IL-10 expression in macrophages and stimulates the polarization of T cells to the Th1 subset. Three promoter polymorphisms of the human Eta-1 gene, -443T/C, -156delG/G, -66T/G, were investigated for possible influence on gene expression. Electrophoretic mobility shift assays (EMSA) with nuclear extract from the human myeloid leukaemia premonocyte cell line, THP-1, revealed sequence specific binding of the transcription factor Sp1 to the -66T allele but not the -66G allele, and haplotype -443C/-156G/-66T showed a marked increase in promoter activity of a luciferase reporter gene. Thus, a substitution of the T-base with G at position -66 in the Eta-1 promoter modulates the promoter activity of the Eta-1 gene, which might influence the Th1 versus Th2 balance. These observations are discussed in relation to a recently reported related observation on the same gene, and it is argued that discrepancies between reporter gene assays in the two studies may be due to the use of different cell lines and may reflect requirements for different transcription factors in cells involved in immune responses compared with other cells.
Mol Immunol 2006 Mar
PMID:A functional polymorphism in the Eta-1 promoter is associated with allele specific binding to the transcription factor Sp1 and elevated gene expression. 1600 26

Bronchiolitis obliterans (BOS - bronchiolitis obliterans syndrome - clinical diagnosis; CBO-histopathologic diagnosis), is a chronic disease process of fibrosis and cellular deposition in airways, complicating long term survival following lung transplantation. BOS is also the result of sporadic toxicant exposure, with airway signs, symptoms, and histology indistinguishable from allograft rejection. This study establishes a transplant BOS model in MHC-mismatched rats and compares their cytokine profiles and histopathology to that of our established toxicant-induced BOS model. Both models result in lung histopathology similar to human disease. Cytokines and inflammation markers that are elevated in human transplant BOS (TGFbeta, iNOS, IFNgamma) were also elevated significantly in both models. Anti-nuclear antibody was absent from all sera in transplant or toxicant models exhibiting advanced airway pathology. The cytokine osteopontin was highly elevated in BAL early in toxicant-induced BOS, but increased late in the transplant-induced BOS model. The data show that BOS is a disease of a pathologic endpoint that is induced by different triggers and processes. The highly elevated BAL osteopontin early in the toxicant-induced BOS model suggests a need for evaluation in the diagnostic setting.
Exp Mol Pathol 2005 Dec
PMID:Transplant-related bronchiolitis obliterans (BOS) demonstrates unique cytokine profiles compared to toxicant-induced BOS. 1622 52

Tissue engineering represents a promising method for generating chondrogenic grafts for reconstructive surgery. In cultured chondrocytes, the dedifferentiation of cells seems unavoidable for multiplication. Stem cells, however, displaying unlimited self-renewal and the capacity to differentiate towards chondrocytes, might be usable after further characterization. As the interactions between the extracellular matrix and the cellular compartment can alter the cellular behaviour, we investigated the expression of integrins using microarray analysis during chondrogenic differentiation of human mesenchymal stem cells (MSC) in comparison with de-differentiating human chondrocytes (HC) harvested during septoplasty. During chondrogenic differentiation of MSC, the fibronectin-receptor (Integrin beta1alpha5), fibronectin and the GPIIb/IIIa-receptor were downregulated. The components of the vitronectin-receptor (Integrin alphavbeta3) and CD47 were constantly expressed and ILK was downregulated. Vitronectin and osteopontin were not expressed by the cells. In HC, Integrin beta1alpha5 in conjunction with the ligand fibronectin were upregulated during dedifferentiation, Integrin alphavbeta3 as well as the GBIIb/IIIa-receptor were activated on day 21 but neither vitronectin nor osteopontin were expressed by the cells. The integrins, beta2, beta4, beta6, beta8 and alpha2, alpha4, alpha6, alpha7, alpha11, were not expressed at any time. ILK, CD47, and ICAP were activated with ongoing dedifferentiation. In conclusion, a candidate for signal-transmission is the fibronectin receptor (integrin alpha5beta1) in conjunction with its ligand fibronectin. Other receptors, e.g. for vitronectin and osteopontin (alphavbeta3), or their ligands do not seem to be involved in signal transmission for dedifferentiation. The GPIIb/IIIa-receptor might assist the process of dedifferentiation. Intracellularly, ILK, ICAP1 and CD47 might be involved in the transduction of integrin-dependent signals.
Int J Mol Med 2006 Feb
PMID:In vitro analysis of integrin expression during chondrogenic differentiation of mesenchymal stem cells and chondrocytes upon dedifferentiation in cell culture. 1639 30

Functional engineering of musculoskeletal tissues generally involves rapid expansion of progenitor cells in vitro while retaining their potential for further differentiation and then induction in specific culture conditions. The autologous adipose-derived stromal cells (ASCs) are considered to contain pluripotent mesenchymal stem cells. Imaging with expression of green fluorescent protein (GFP) facilitates the detailed research on ASCs physiological behavior during differentiation into a variety of cell lineages both in vitro and in vivo. In this study, we aimed to confirm the trans-germ plasticity of homogeneously marked ASCs from GFP transgenic mice. Simultaneously, the term and intensity of GFP expression in ASCs were also focused on during variant inductions, when cells were incubated with multiple growth factors and adjuvant. ASCs were harvested from inguinal fat pads of transgenic nude mice, passaged 3 times in monolayer cultures, and then transferred to osteogenic, adipogenic, neurogenic, and myogenic medium. The morphological characterization of inductive cells was observed using phase-contrast microscopy and histological staining such as alizarin red for mineralization nodules and oil red O for lipid accumulation. The expression of marker genes or proteins was measured using RT-PCR and immunocytochemical analysis. Collagen type I, osteopontin (OPN), and osteocalcin (OCN) were positive in osteogenic lineages, peroxisome proliferator-activated receptor(PPAR)-gamma2 and lipoprotein lipase (LPL) were positive in adipogenic ones, glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) were positive in neurogenic ones, and alpha-smooth muscle actin (alpha-SMA) was positive in myogenic ones. Moreover, the results of fluorescence microscopic imaging suggested that there was no significant decline of GFP expression during ASCs differentiation and the level of GFP maintained stable till differentiated ASCs showed apoptotic phenotype. So the endogenous GFP and multilineage potential of transgenic ASCs had no influences on each other. Since the population of GFP ASCs can be easily identified, it is proposed that they may be promising candidate seed cells for further studies on ASCs tissue engineering, especially the study on engineered tissues formed in vivo.
Mol Cell Biochem 2006 Apr
PMID:Multilineage differentiation of adipose-derived stromal cells from GFP transgenic mice. 1647 77

The interaction between prostate cancer cells and bone marrow stromal cells (BMSC) is critical for survival and proliferation of metastatic cancer cells in the bone microenvironment. In order to study molecular mechanisms of prostate cancer bone metastasis, we established a novel heterotypic co-culture system, in which the role of direct cell-cell contact between prostate cancer cells and BMSC in addition to soluble factors can be analyzed. Using both bi-compartmental (insert) system and heterotypic (contact) system, we identified gene expression profiles of interaction between prostate cancer and bone cells. Analysis of differential gene expressions in these two co-culture systems revealed three distinctive sets of genes: 1) genes that were modified only by soluble factors; 2) genes that were regulated by both soluble factors and physical contact; and 3) genes that were altered only by physical contact. The last group consisted of specific set of genes including collagen III, IV, X, XII, integrin alpha1, alpha2, MMP-2, MMP-9, uPA, biglycan, osteopontin and raf-1 in PC3, and collagen VIII, IX, BMP6, TGFbeta1, Smad6 and Twist in BMSC. Among genes that were modified by both soluble factors and physical contact, the gene expression was affected in the same direction (such as MKK4) or in the opposite direction (such as TGFbeta receptor 3). Overall, this suggests that heterotypic cell-cell contact may act as an independent factor affecting the progression of bone metastasis.
Int J Mol Med 2006 May
PMID:Identification of a unique set of genes altered during cell-cell contact in an in vitro model of prostate cancer bone metastasis. 1659 70

Musculoskeletal tissues regeneration requires rapid expansion of seeding cells both in vitro and in vivo while maintaining their multilineage differentiation ability. Human adipose-derived stem cells (ASCs) are considered to contain multipotent mesenchymal stem cells. Monolayer cultures of human ASCs were isolated from human lipoaspirates and passaged 3 times and then infected with replication-incompetent adenoviral vectors carrying green fluorescent protein (Ad/GFP) genes. Then, Ad/GFP infected human ASCs were transferred to osteogenic, chondrogenic, adipogenic, and myogenic medium. The morphological characterization of induced cells was observed using phase-contrast microscopy and fluorescence microscopy. The expression of marker proteins or genes was measured by immunocytochemical and RT-PCR analysis. Osteopontin (OPN), and osteocalcin (OCN) were positive in osteogenic lineages, aggrecan and SOX9 were positive in chondrogenic ones, peroxisome proliferator-activated receptor (PPAR-gamma2) and lipoprotein lipase (LPL) were positive in adipogenic ones, and myogenin and myod1 was positive in myogenic ones. At the same time, the results of fluorescence microscopic imaging proved that the high level of GFP expression during ASCs differentiation maintained stable nearly 2 months. So the exogenous GFP and multilineage potential of human ASCs had no severe influences on each other. Since the human ASCs can be easily obtained and abundant, it is proposed that they may be promising candidate cells for further studies on tissue engineering. Imaging with expression of GFP facilitates the research on ASCs physiological behavior and application in tissue engineering during differentiation both in vitro and in vivo.
Mol Cell Biochem 2006 Oct
PMID:Pluripotency potential of human adipose-derived stem cells marked with exogenous green fluorescent protein. 1671 63

In addition to its calciotropic function, the secosteroid 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has potent anti-proliferative/immunomodulatory effects on various tissues. Consistently, the enzyme that catalyzes the synthesis of 1,25(OH)(2)D(3), 1alpha-hydroxylase (1alpha-OHase) and the vitamin D receptor have a widespread tissue distribution. Among site-specific functions, the hormone has been suggested to be involved in uterine physiology. However, molecular analysis of the vitamin D system in normal endometrium throughout the menstrual cycle as well as its regulation in the context of endometrial physiological and pathological events have received very limited attention. Thus, we have studied expression, localization and regulation of 1alpha-OHase in human cycling and early pregnant endometrium. The capacity for 1alpha-hydroxylation and the presence of vitamin D receptor in endometrial cells have also been evaluated. The functional significance of these findings has been tested by evaluating gene expression of the catabolic enzyme, vitamin D 24-hydroxylase, and of the adhesion protein, osteopontin. Finally, to verify any potential dysfunction of the vitamin D system in endometriosis, a reproductive disease characterized by immune-mediated anomalies, we have analyzed expression of 1alpha-OHase in both eutopic and ectopic endometrium of affected patients. Results obtained showed that the active form of the 1alpha-OHase gene was expressed in human endometrial stromal cells independent of the cycle phase but with a significant increase in early pregnant decidua. A similar profile was observed for the protein, which was abundantly expressed in the cytoplasm of both endometrial stroma and epithelial glands. Both cycling and early pregnant endometrial cells also expressed the vitamin D receptor. In the same cells, 1alpha-OHase mRNA levels were significantly stimulated by the pro-inflammatory cytokine interleukin (IL)-1beta (50 and 500 pg/ml) while addition of the active form of the hormone could modulate both CYP24 and osteopontin gene expression. The 1alpha-OHase gene was also expressed in ectopic endometrium and its levels were increased in proliferative phase cultures derived from patients with endometriosis. Human cycling endometrium may be included among the extrarenal sites able to synthesize vitamin D. The IL-1beta-mediated induction of 1alpha-OHase gene and the hormonal modulation of osteopontin support a role for the hormone in the immunological mechanisms underlying uterine function. Abnormalities of this system are present in endometriosis.
J Mol Endocrinol 2006 Jun
PMID:Cycling and early pregnant endometrium as a site of regulated expression of the vitamin D system. 1672 Jul 13

Osteogenesis is a complex process associated with dramatic changes in gene expression. To elucidate whether modifications in chromatin structure are involved in osteoblast differentiation, we examined the expression levels of histone deacetylases (HDACs) and the degree of histone acetylation at the promoter regions of osteogenic genes. During osteogenesis, total HDAC enzymatic activity was decreased with significant reduction in HDAC1 expression. Consistently, recruitment of HDAC1 to the promoters of osteoblast marker genes, including osterix and osteocalcin, was down-regulated, whereas histone H3 and H4 were hyperacetylated at those promoters during osteoblast differentiation. Moreover, suppression of HDAC activity with a HDAC inhibitor, sodium butyrate, accelerated osteogenesis by inducing osteoblast marker genes including osteopontin and alkaline phosphatase. Consistently, knockdown of HDAC1 by the short interference RNA system stimulated osteoblast differentiation. Taken together, these data propose that down-regulation of HDAC1 is an important process for osteogenesis.
Mol Endocrinol 2006 Oct
PMID:Histone deacetylase 1-mediated histone modification regulates osteoblast differentiation. 1672 31


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