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)

Gicerin, an Ig-superfamily cell adhesion molecule, appears transiently in embryonic tissues including those of the nervous, urogenital, respiratory and digestive systems, and it promotes neurite extension, cell migration and epithelialization through its cell adhesive activities. In addition, gicerin also reappears in regenerating tissue after suffering either a traumatic injury or a viral infection. In the present study, we examined the expression pattern of gicerin in the regeneration of hepatocytes. Immunohistochemically, gicerin protein appeared in the regenerating hepatocytes of carbon tetrachloride (CCl4)-induced acute hepatitis, while it was scarcely expressed in the hepatocytes of normal mouse liver. Real-time PCR revealed the up-regulation of gicerin transcription in the regenerating process of CCl4-induced hepatitis. The expression of transforming growth factor (TGF)-beta1 was also increased during the regeneration. Furthermore, the gicerin mRNA expression increased during the process of an in vitro hepatocyte regeneration model using mouse primary hepatocytes and hepa 1-6 cells. To note, the mRNA levels of gicerin in these cells were enhanced by the presence of TGF-beta1. Collectively, these findings suggest that TGF-beta1 may therefore regulate gicerin expression in hepatocytes leading to liver regeneration by cell-cell or cell-ECM interactions.
Int J Mol Med 2007 Mar
PMID:Involvement of transforming growth factor-beta in the expression of gicerin, a cell adhesion molecule, in the regeneration of hepatocytes. 1727 84

Changes in the ECM and increased airway smooth muscle (ASM) mass are major contributors to airway remodeling in asthma and chronic obstructive pulmonary disease. It has recently been demonstrated that ECM proteins may differentially affect proliferation and expression of phenotypic markers of cultured ASM cells. In the present study, we investigated the functional relevance of ECM proteins in the modulation of ASM contractility using bovine tracheal smooth muscle (BTSM) preparations. The results demonstrate that culturing of BSTM strips for 4 days in the presence of fibronectin or collagen I depressed maximal contraction (E(max)) both for methacholine and KCl, which was associated with decreased contractile protein expression. By contrast, both fibronectin and collagen I increased proliferation of cultured BTSM cells. Similar effects were observed for PDGF. Moreover, PDGF augmented fibronectin- and collagen I-induced proliferation in an additive fashion, without an additional effect on contractility or contractile protein expression. The fibronectin-induced depression of contractility was blocked by the integrin antagonist Arg-Gly-Asp-Ser (RGDS) but not by its negative control Gly-Arg-Ala-Asp-Ser-Pro (GRADSP). Laminin, by itself, did not affect contractility or proliferation but reduced the effects of PDGF on these parameters. Strong relationships were found between the ECM-induced changes in E(max) in BTSM strips and their proliferative responses in BSTM cells and for E(max) and contractile protein expression. Our results indicate that ECM proteins differentially regulate both phenotype and function of intact ASM.
Am J Physiol Lung Cell Mol Physiol 2007 Jun
PMID:Extracellular matrix proteins differentially regulate airway smooth muscle phenotype and function. 1729 76

Patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF) and bronchopulmonary dysplasia (BPD), suffer from lung fibrosis secondary to myofibroblast-mediated excessive ECM deposition and destruction of lung architecture. Transforming growth factor (TGF)-beta1 induces epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AEC) to myofibroblasts both in vitro and in vivo. Inhaled nitric oxide (NO) attenuates ECM accumulation, enhances lung growth, and decreases alveolar myofibroblast number in experimental models. We therefore hypothesized that NO attenuates TGF-beta1-induced EMT in cultured AEC. Studies of the capacity for endogenous NO production in AEC revealed that endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) are expressed and active in AEC. Total NOS activity was 1.3 pmol x mg protein(-1) x min(-1) with 67% derived from eNOS. TGF-beta1 (50 pM) suppressed eNOS expression by more than 60% and activity by 83% but did not affect iNOS expression or activity. Inhibition of endogenous NOS with l-NAME led to spontaneous EMT, manifested by increased alpha-smooth muscle actin (alpha-SMA) expression and a fibroblast-like morphology. Provision of exogenous NO to TGF-beta1-treated AEC decreased stress fiber-associated alpha-SMA expression and decreased collagen I expression by 80%. NO-treated AEC also retained an epithelial morphology and expressed increased lamellar protein, E-cadherin, and pro-surfactant protein B compared with those treated with TGF-beta alone. These findings indicate that NO serves a critical role in preserving an epithelial phenotype and in attenuating EMT in AEC. NO-mediated regulation of AEC fate may have important implications in the pathophysiology and treatment of diseases such as IPF and BPD.
Am J Physiol Lung Cell Mol Physiol 2007 Jul
PMID:Nitric oxide attenuates epithelial-mesenchymal transition in alveolar epithelial cells. 1749 59

Filamin B (FLNB) is a cytoplasmic protein that regulates the cytoskeletal network by cross-linking actin, linking cell membrane to the cytoskeleton and regulating intracellular signaling pathways responsible for skeletal development (Stossel, T.P., Condeelis, J., Cooley, L., Hartwig, J.H., Noegel, A., Schleicher, M. and Shapiro, S.S. (2001) Filamins as integrators of cell mechanics and signalling. Nat. Rev. Mol. Cell Biol., 2, 138-145). Mutations in FLNB cause human skeletal disorders [boomerang dysplasia, spondylocarpotarsal (SCT), Larsen, and atelosteogenesis I/III syndromes], which are characterized by disrupted vertebral segmentation, joint formation and endochondral ossification [Krakow, D., Robertson, S.P., King, L.M., Morgan, T., Sebald, E.T., Bertolotto, C., Wachsmann-Hogiu, S., Acuna, D., Shapiro, S.S., Takafuta, T. et al. (2004) Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat. Genet., 36, 405-410; Bicknell, L.S., Morgan, T., Bonafe, L., Wessels, M.W., Bialer, M.G., Willems, P.J., Cohn, D.H., Krakow, D. and Robertson, S.P. (2005) Mutations in FLNB cause boomerang dysplasia. J. Med. Genet., 42, e43]. Here we show that Flnb deficient mice have shortened distal limbs with small body size, and develop fusion of the ribs and vertebrae, abnormal spinal curvatures, and dysmorphic facial/calvarial bones, similar to the human phenotype. Characterization of the mutant mice demonstrated increased apoptosis along the bone periphery of the distal appendages, consistent with reduced bone width. No changes in the initial proliferative rate of chondrocytes were observed, but the progressive differentiation of chondrocyte precursors was impaired, consistent with reduced bone length. The extracellular matrix appeared disrupted and phosphorylated beta1-integrin (a collagen receptor and Flnb binding partner) expression was diminished in the mutant growth plate. Like integrin-deficient chondrocytes, adhesion to the ECM was decreased in Flnb(-/-) chondrocytes, and inhibition of beta1-integrin in these cells led to further impairments in cell spreading. These data suggest that disruption of the ECM-beta1-integrin-Flnb pathway contributes to defects in vertebral and distal limb development, similar to those seen in the human autosomal recessive SCT due to Flnb mutations.
Hum Mol Genet 2007 Jul 15
PMID:Filamin B mutations cause chondrocyte defects in skeletal development. 1751 Feb 10

Ovulation is a complex process of releasing a fertilizable oocyte and depends on the proper formation of an extracellular hyaluronan rich matrix by the cumulus oocyte complex (COC). The formation of a HA rich matrix is dependent on the synthesis and organization of HA in the presence of several biomolecules that mediate its crosslinking. To gain an insight into the follicular maturation and COC expansion, we have studied the expression of hyaluronan binding protein 1 (HABP1), which is known to interact specifically with hyaluronan. The level of HABP1 increased markedly during ovulation after gonadotropin stimulation, and the overexpression was seen in mural granulosa cells, expanding cumulus cells and follicular fluid. However, HABP1 could not be detected in the luteal cells of corpus luteum after ovulation. Such increased expression of HABP1 was observed both during in vivo and in vitro conditions of COC expansion. The level of HABP1 transcript was upregulated up to fivefold after COC expansion as compared to compact COC. Immunofluorescence analysis showed HABP1 to be localized in the cytoplasm and extracellular matrix, suggesting its role in ECM organization. The cultured expanded COC treated with hyaluronidase for different time periods showed the gradual dispersion of COC, which coincide with the loss of HABP1 from the matrix suggesting that HABP1 is bound to hyaluronan. These results indicate that HABP1 expressed in rat COCs during maturation may facilitate the formation of the HA matrix in the extracellular space around the oocyte with cumulus expansion during maturation.
Mol Reprod Dev 2008 Mar
PMID:Higher expression of hyaluronan binding protein 1 (HABP1/p32/gC1qR/SF2) during follicular development and cumulus oocyte complex maturation in rat. 1756 59

The aim of this study was to investigate the immunohistochemical distribution of laminin, vimentin and desmin during the implantation period in the rat since ECM remodelling and the expression of intermediate filaments (Ifs) is essential for successful decidualization and implantation. On day 4 of pregnancy, laminin was found in a few endometrial stromal cells (ESC), the basement membrane of the numerous endometrial blood vessels, in endometrial glands and as well as in the uterine epithelium. The localization of vimentin on day 4 of pregnancy was widespread in the ESC. However, desmin immunoreactivity was low in ESC on this day of pregnancy. On day 6 of pregnancy, laminin and vimentin were localized in the decidual area underlying luminal epithelium and around the implanting embryo. Additionally, desmin was found to be present densely in decidual cells of the anti-mesometrial region where implantation takes place. Finally, on day 8 of pregnancy, laminin was present in decidual and parietal endodermal cells, whereas vimentin was immunolocalized in primary and secondary decidual regions in the endometrium. In contrast, desmin was detected in some parts of the secondary decidual zone. In conclusion, these proteins could have crucial roles in decidualization and implantation.
J Mol Histol 2007 Aug
PMID:Distribution of laminin, vimentin and desmin in the rat uterus during initial stages of implantation. 1765 7

Fibroblast growth factors (FGFs) play critical roles in development, maintenance, and repair following injury or disease in the lung. Their activity is modulated by a variety of factors, including FGF-binding protein (FGF-BP; HBp-17) and N-deacetylase/N-sulfotransferase-1 (NDST-1). Functionally, FGF-BP shuttles FGFs from binding sites in ECMs to cell surfaces and enhances FGF binding and signaling, whereas NDST-1 adds sulfate groups to FGF coreceptor proteoglycans and modulates alveolar type II (ATII) cell maturation and differentiation. Since the sulfated nature of ECMs is a critical determinant of their relationship with FGFs, we predicted that ECMs and their sulfation would modulate the expression of FGF-BP and NDST-1. To examine this question, selected culture conditions of rat ATII cells were manipulated [with and without coculture with rat lung fibroblasts (RLFs)] by treatment with heparin or sodium chlorate (inhibitor of sulfation) for 24-96 h. In addition, ECMs biosynthesized by RLFs for up to 10 days before coculture were used as model intervening barriers to communication between alveolar cells and fibroblasts. FGF-BP expression was enhanced in ATII cells by coculture with RLF cells and least suppressed by desulfated heparin. NDST-1 expression in ATII cells was most sensitive to the amount of sulfation in medium and ECM and enhanced by fully sulfated heparin. Preformed ECM appears to supply factors that modify subsequent treatment effects. These results demonstrate a potentially important modulatory influence of sulfated ECMs and fibroblasts on FGF-BP and NDST-1 at the gene expression level.
Am J Physiol Lung Cell Mol Physiol 2007 Nov
PMID:Fibroblast growth factor-binding protein and N-deacetylase/N-sulfotransferase-1 expression in type II cells is modulated by heparin and extracellular matrix. 1776 86

Lung fibrosis is characterized by increased deposition of ECM, especially collagens, and enhanced proliferation of fibroblasts. l-arginine is a key precursor of nitric oxide, asymmetric dimethylarginine, and proline, an amino acid enriched in collagen. We hypothesized that l-arginine metabolism is altered in pulmonary fibrosis, ultimately affecting collagen synthesis. Expression analysis of key enzymes in the arginine pathway, protein arginine methyltransferases (Prmt), arginine transporters, and arginases by quantitative (q) RT-PCR and Western blot revealed significant upregulation of arginase-1 and -2, but not Prmt or arginine transporters, during bleomycin-induced pulmonary fibrosis in mice. HPLC revealed a concomitant, time-dependent decrease in pulmonary l-arginine levels. Arginase-1 and -2 mRNA and protein expression was increased in primary fibroblasts isolated from bleomycin-treated mice, compared with controls, and assessed by qRT-PCR and Western blot analysis. TGF-beta1, a key profibrotic mediator, induced arginase-1 and -2 mRNA expression in primary and NIH/3T3 fibroblasts. Treatment of fibroblasts with the arginase inhibitor, NG-hydroxy-l-arginine, attenuated TGF-beta1-stimulated collagen deposition, but not collagen mRNA expression or Smad signaling, in fibroblasts. In human lungs derived from patients with idiopathic pulmonary fibrosis, arginase activity was unchanged, but arginase-1 expression significantly decreased when compared with donor lungs. Our results thus demonstrate that arginase-1 is expressed and functionally important for collagen deposition in lung fibroblasts. TGF-beta1-induced upregulation of arginase-1 suggests an interplay between profibrotic agents and l-arginine metabolism during the course of lung fibrosis in the mouse, whereas species-specific regulatory mechanisms may account for the differences observed in mouse and human.
Am J Physiol Lung Cell Mol Physiol 2008 Jan
PMID:Functional role and species-specific contribution of arginases in pulmonary fibrosis. 1793 65

MMPs are endopeptidases that play a pivotal role in ECM turnover. RECK is a single membrane-anchored MMP-regulator. Here, we evaluated the temporal and spatial expression of MMP-2, MMP-9, and RECK during alveolar bone regeneration. The maxillary central incisor of Wistar rats was extracted and the animals were killed at 1, 3, 7, 10, 14, 21, 28, and 42 days post-operatively (n = 3/period). The hemimaxillae were collected, demineralized and embedded in paraffin. Immunohistochemical analysis was performed by the immunoperoxidase technique with polyclonal antibodies. On day 1, polymorphonuclear cells in the blood clot presented mild immunolabeling for MMPs. During bone remodeling, osteoblasts facing new bone showed positive staining for gelatinases and RECK in all experimental periods. MMPs were also found in the connective tissue and endothelial cells. Our results show for the first time that inactive and/or active forms of MMP-2, MMP-9 and RECK are differentially expressed by osteogenic and connective cells during several events of alveolar bone regeneration. This may be important for the replacement of the blood clot by connective tissue, and in the formation, maturation and remodeling of new bone.
J Mol Histol 2008 Apr
PMID:Expression of matrix metalloproteinases-2 and -9 and RECK during alveolar bone regeneration in rat. 1798 94

Fibrotic progression of chronic liver diseases of different aetiology to the common advanced-stage of cirrhosis can be envisaged as a dynamic and highly integrated cellular response to chronic liver injury. Liver fibrosis is accompanied by perpetuation of liver injury, chronic hepatitis and persisting activation of tissue repair mechanisms, leading eventually to excess deposition of ECM components. Liver fibrogenesis (i.e., the process) is sustained by populations of highly proliferative, pro-fibrogenic and contractile MFs that, according to current literature, originate by a process of activation involving perisinusoidal HSC, portal fibroblasts and even bone marrow-derived MSC. In this short review emerging concepts in hepatic fibrogenesis and related molecular mechanisms, as provided by recent experimental and clinical studies, are presented.
Mol Aspects Med
PMID:Myofibroblast - like cells and liver fibrogenesis: Emerging concepts in a rapidly moving scenario. 1802 82


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