Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies demonstrated that corneal epithelial cells isolated without basal lamina respond to extracellular matrix (ECM) in an actin dependent manner; the basal cell surface flattens and the actin cortical mat reorganizes. We hypothesize that the actin reorganization is initiated by intracellular signaling mechanisms that includes tyrosine phoshporylation and activation of the Rho, MAP kinase, and PI3 kinase signal transduction pathways. Our goals were to develop a morphological assay to test this hypothesis by answering the following questions: 1) Do the actin bundle formations in the cortical mat have the same configuration in response to different ECM molecules? 2) What is the minimum time ECM molecules need to be in contact with the tissue for the actin to reorganize? 3) Will blocking tyrosine phosphorylation inhibit reorganization of the actin? 4) Are known signal transduction proteins phosphorylated in response to soluble matrix molecules? The actin cortical mat demonstrated distinct bundle configurations in the presence of different ECM molecules. Soluble fibronectin accumulated at the basal cell surfaces 75-fold over 30 min in a clustered pattern. The cells need contact with ECM for a minimum of 10 min to reform the actin bundles at 2 hr. In contrast, two substances that bind to heptahelical receptors to stimulate the Rho pathway, bombesin and lysophosphatidic acid, reorganized the actin bundles in 15-30 min. Focal adhesion kinase, p190 Rho-GAP, tensin, and paxillin were tyrosine phosphorylated in response to soluble fibronectin, type I collagen, or laminin 1. Erk-1, erk-2, and PI3 kinase were activated after 1 hr stimulation by type I collagen. Herbimycin A blocked actin reorganization induced by ECM molecules. In conclusion, we have developed two morphological assays to examine the response of corneal epithelial cells to ECM molecules. In addition, actin bundle reorganization involved tyrosine phosphorylation, MAP kinase, and PI3 kinase activation.
Anat Rec 1999 03
PMID:ECM-stimulated actin bundle formation in embryonic corneal epithelia is tyrosine phosphorylation dependent. 1009 66

Convulxin (Cvx) isolated from Crotalus durissus terrificus venom selectively binds with a high affinity to platelets and induces platelet aggregation by a mechanism that resembles that induced by collagen. Taking advantage that P65 has been recently cloned and expressed as a recombinant soluble protein (rec-P65), we examined the role of this non-integrin collagen receptor in platelet activation induced by Cvx. Rec-P65 blocked platelet adhesion to collagen-coated surfaces and inhibited platelet aggregation and ATP secretion induced by type I collagen. On the other hand, rec-P65 did not inhibit platelet aggregation and ATP secretion induced by Cvx, and it did not affect platelet adhesion to Cvx. In addition, ligand-blotting indicated that the Cvx binding to the collagen receptor GPVI was preserved in the presence of rec-P65. These observations indicate that P65 does not play a significant role in platelet activation by Cvx; in contrast, platelet response to collagen involves multiple receptors.
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PMID:Role of the recombinant non-integrin platelet collagen receptor P65 on platelet activation induced by convulxin. 1077 28

Children suffering from thalassaemia major are reported to have growth delay and bone alterations even when well transfused and chelated. In the present study we evaluated bone and collagen turnover (bone Gla-protein, BGP; carboxyterminal telopeptide of type I collagen, ICTP; aminoterminal propeptide of type III procollagen, PIIINP, respectively) and bone mineral density (BMD) in 5 pre-pubertal GH deficient thalassaemic children before and during rec-GH treatment (0.6 IU/kg/week). Data were compared with those recorded in an age- and sex-matched control group. Before treatment, serum BGP and ICTP levels were significantly lower (p<0.0001) in children with thalassaemia (9.3+/-0.7 ng/ml and 5.3+/-0.5 ng/ml, respectively) than in healthy controls (18.9+/-0.9 ng/ml and 14.4+/-0.6 ng/ml, respectively), while serum PIIINP levels did not significantly differ in the two groups (6.7+/-0.7 ng/ml vs 6.7+/-0.7 ng/ml). Mean lumbar BMD values of patients (0.62+/-0.05 g/cm2) were significantly lower (p<0.05) than those recorded in healthy controls (0.78+/-0.01 g/cm2), while femoral BMD values were similar in the two groups (patients: 0.70+/-0.08 g/cm2 vs controls: 0.74+/-0.01 g/cm2). One-year GH therapy significantly increased height velocity (from 2.3+/-0.2 cm/year to 6.1+/-0.4 cm/yr, p<0.0001) and IGF-I levels (from 61.6+/-15.4 to 342+/-38.5 ng/ml, p<0.005). Serum BGP (basal: 9.3+/-0.7 ng/ml, 6th month: 10.8+/-0.6 ng/ml, 12th month: 14.9+/-1.4 ng/ml), ICTP (basal: 5.3+/-0.5 ng/ml, 6th month: 7.9+/-0.8 ng/ml, 12th month: 10.9+/-1.7 ng/ml) and PIIINP levels (basal: 6.7+/-0.7 ng/ml, 6th month: 9.9+/-1.0 ng/ml, 12th month: 9.6+/-1.4 ng/ml) significantly increased (p<0.05), while no significant effects were observed on lumbar and femoral BMD values. Although the GH-induced stimulation of bone turnover markedly increased BGP (+60%) and ICTP (+105%) levels, one-year GH therapy was not sufficient to completely normalize these parameters, which remained significantly lower than in healthy controls. In conclusion, our study shows that pre-pubertal GH deficient children with thalassaemia major have reduced bone turnover (both bone formation and resorption) and lumbar BMD values, thus indicating that bone metabolism should be monitored and improved even in well-transfused patients. One-year GH treatment is able to increase, but not normalize, bone turnover, this effect being insufficient to improve BMD values. More prolonged periods of GH therapy are probably requested to positively affect both bone turnover and BMD values in GH deficient thalassaemic patients, as occurs in children and adults with GH deficiency.
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PMID:Effects of 12 months rec-GH therapy on bone and collagen turnover and bone mineral density in GH deficient children with thalassaemia major. 1090 62

Serum bone-Gla protein (BGP), bone alkaline phosphatase (B-AP), and C-terminal cross-linked telopeptide of type I collagen (ICTP) levels were evaluated in 18 adults with acquired GH deficiency (GHD, 14 males and 4 females, age range: 25-59 yr) before, at 3, 6, 9 and 12 months of rec-GH treatment (0.125 IU/kg/week for the first month, followed by 0.25 IU/kg/week for 11 months) and 6 months after the withdrawal of therapy. Total body bone mineral density (BMD, g/cm2) was measured with dual energy X-ray absorptiometry (Hologic QDR 1000/W) before, at 12 months of GH treatment and 6 months after its withdrawal. Before treatment, BGP (mean+/-SE: 5.1+/-0.4 ng/ml), B-AP (59.4+/-6.5 IU/l), ICTP (3.1+/-0.3 ng/ml) levels of patients were similar to in healthy controls (BGP: 5.4+/-0.1 ng/ml; B-AP: 58.2+/-2.0 IU/l; ICTP: 4.1+/-0.3 ng/ml). GH treatment caused a significant increase of BGP, B-AP, ICTP levels, the maximal stimulation of bone resorption, occurring after 3 months of GH treatment, while the maximal effect on bone formation being evident later (at 6th month). A slight decline in BGP, B-AP, T-AP and ICTP levels occurred at 9-12 months of therapy, although the values remained significantly higher than in basal conditions and with respect to healthy controls. Before treatment, mean total body BMD of patients (1.110+/-0.027 g/cm2, range: 0.944-1.350 g/cm2) was not significantly different (z-score: +0.47+/-0.31, NS) from that observed in healthy controls (1.065+/-0.008 g/cm2, range: 1.008-1.121 g/cm2). GH therapy was associated with a significant reduction of mean total body BMD values (6th month: -1.8+/-0.5%, p<0.01; 12th month: -2.1+/-1.0%, p<0.05 vs baseline), particularly evident in the first six months of treatment. Six months after the withdrawal of GH therapy, BGP (5.9+/-0.5 ng/ml), B-AP (57.3+/-7.0 IU/l) and ICTP (3.2+/-0.1 ng/ml) levels returned similar to those recorded before treatment, while total BMD increased (+1.5+/-0.7, p<0.05), remaining however slightly lower than in basal conditions (-0.6+/-1.2, NS). In conclusion, our study shows that: a) acquired GHD in adulthood is associated with both normal bone formation/resorption indexes and normal total body BMD; b) GH therapy causes a significant rise of bone formation/resorption markers (earlier and greater for bone resorption); c) one-year GH therapy is associated with a reduction of total body BMD values, particularly evident in the first 6 months of treatment; d) the effects of GH therapy on bone turnover are transient, being completely reverted six months after the withdrawal of GH therapy; e) the increase of total body BMD (up to baseline values) after GH withdrawal might be explained as consequence of persisting effects of previous GH stimulation on bone remodeling.
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PMID:Effects of 12-month GH treatment on bone metabolism and bone mineral density in adults with adult-onset GH deficiency. 1138 8

The periosteum contains osteoprogenitors that differentiate to osteoblasts in bone growth or repair. Our previous studies suggested the hypothesis that the physical contact of the periosteum with the bone matrix is requisite for the differentiation of osteoblasts. To test the hypothesis, the present study was designed to investigate how the contact between the periosteum and the bone matrix influences the osteoblastic differentiation of periosteal cells with establishing a new experimental model in vivo. Differentiation of osteoblasts was assessed by gene expression of type I collagen, osteocalcin and bone sialoprotein using in situ hybridization. A barrier was designed to prevent periosteal cells from contacting the bone matrix using the membrane filter. The membrane filter was inserted surgically between the surface of rat parietal bone and the periosteum after being punched out with pin holes. Periosteal cells were allowed to contact with the bone surface only through the pin holes. The pin hole was filled with cells derived from the periosteum 1 week after inserting the filter. Differentiation of osteoblasts in week 2 and noticeable bone formation in week 3 were identified on the bone surface only under the pin hole but not under the filter. The present study demonstrated that the physical contact with the bone matrix promotes osteoblastic differentiation of periosteum-derived cells in vivo.
Anat Rec 2001 09 01
PMID:Osteoblastic differentiation of periosteum-derived cells is promoted by the physical contact with the bone matrix in vivo. 1150 73

Although hypoxic and/or nutritional insults during gestation are believed to contribute to congenital heart defects, the mechanisms responsible for these anomalies are not understood. Given the role vascular endothelial growth factor (VEGF) plays in response to hypoxia, it is a likely candidate for mediating deleterious effects of embryonic hypoxia. The ectopic or overproduction of endogenous factors such as VEGF may contribute to specific heart defects. Here we compared hypoxia-induced precocious production of VEGF during early heart valve development to normal VEGF production. Mouse prevalvular cardiac endocardial cushions were explanted onto hydrated type I collagen gels under normoxic or hypoxic conditions. The extent of transformation of cardiac endothelium into mesenchyme was inversely correlated with the levels of VEGF during the various culture conditions. A soluble VEGF antagonist confirmed that endogenous production of VEGF was specific for blocking normal cushion mesenchyme formation. We further demonstrated that E10.5 endocardium retains the ability to transform into cardiac mesenchyme in the absence of endogenous VEGF.
Anat Rec A Discov Mol Cell Evol Biol 2003 Mar
PMID:VEGF modulates early heart valve formation. 1255 36

Our previous studies suggested that a part of bone extracellular matrix (ECM) molecules are degraded and remodeled during embryonic bone formation. In contrast, little is known about ECM remodeling in postnatal appositional bone formation. The present study was designed to investigate expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) during experimentally initiated appositional bone formation in rats. Expressions of ECM molecules, MMPs, and TIMPs were examined using in situ hybridization. Osteoblasts and osteocytes expressed MMP2 and -8, TIMP1, -2, and -3, as well as type I collagen, osteopontin, and osteocalcin in the course of the appositional bone formation, while they showed few transcripts of MMP13. The results indicated that while osteoblasts and osteocytes in the apposed bone produce ECM molecules, they degrade ECM molecules with MMPs and regulate the degradation by inhibiting the activity of MMPs using TIMPs. Osteoblasts and osteocytes may reorganize the ECM composition to mature the bone matrix in appositional bone formation.
Anat Rec A Discov Mol Cell Evol Biol 2004 Apr
PMID:Osteoblasts and osteocytes express MMP2 and -8 and TIMP1, -2, and -3 along with extracellular matrix molecules during appositional bone formation. 1505 53

Since Rinehart and Farquhar reported the presence of agranulated cells in the anterior pituitary gland in 1953, the functions of the folliculo-stellate cell remain to be clarified. Intercellular junctions have been described in the monkey, rat, and teleost anterior pituitary glands, indicating the existence of cell-to-cell communication within the organ. We pointed to their possible role in the rapid dissemination of information through a complex interconnecting system of follicles involving gap junctions. The gap junctional/folliculo-stellate cellular network was essential in the maturation and regulation of the pituitary gland system such as the hypothalamic-pituitary-gonadal axis. It has been was shown that a network participated in the conduction of electrophysiological information over a long distance using the ion Ca(++), which propagates to other folliculo-stellate cells by signaling through gap junctions. Sixty-day-old male rats were used in this study for light microscopic immunohistochemistry of S-100 protein, type I collagen, and connexin 43, and for electron microscopy to observe the morphological relationships between the cellular networks of folliculo-stellate cells and granulated pituitary cells. Clusters of anti-S-100 protein-positive cells were clearly observed in a region of the hypophysis tentatively named the transition zone. Anti-S-100 protein-positive cells and their cytoplasmic processes were also present in the anterior lobe and assembled together to form follicular lumina. Type I collagen was clearly shown outlining the incomplete lobular or ductule-like structure making cell cords in the anterior pituitary gland. Numerous microvilli were present within the follicular lumen while around the lumina, junctional specializations including gap junctions were positive for the connexin 43 protein. A nonuniform distribution of the connexin 43-positive sites were observed. Small or dot-shaped positive sites were noted where two clusters of cells were connected; the cells were identified as S-100 cells. Double immunohistochemical staining of the connexin 43 and growth hormone (GH) or connexin 43 and luteinizing hormone (LH) was also performed, demonstrating no direct relationship between the connexin 43 and either the GH or LH cells. These findings indicate that there are two kinds of messages necessary for the hormone release in the pituitary gland. One is via the portal vein system, the other is through the gap junction-mediated networks of folliculo-stellate cells. The granulated cells directly associate with cell membrane of folliculo-stellate cells are able to discharge secretory granules through communication via gap junctions, while those granulated cells that are more distant from the folliculo-stellate cells are only able to discharge hormones via the pituitary hormone-releasing hormone from the portal vein system.
Anat Rec A Discov Mol Cell Evol Biol 2004 May
PMID:Intercellular communication within the rat anterior pituitary gland: X. Immunohistocytochemistry of S-100 and connexin 43 of folliculo-stellate cells in the rat anterior pituitary gland. 1510 42

A detailed study of so-called communicating cartilage canals, which penetrate deeply up into the lower hypertrophic zone of the epiphyseal growth plate in the embryonic chicken femur (E20), was carried out with the aim to clarify whether or not these canals are involved in the bone-forming process. In addition, we examined the manner in which cartilage canals are formed and compare the present data with our previous data. The canals were investigated by means of light microscopy, electron microscopy, immunohistochemistry (VEGF, VEGFR2/Flk1, type I collagen), and 3D reconstruction. Some communicating canals deeply penetrate into the upper hypertrophic zone where they terminate, showing electron-dense cells at their end. Subcellular characteristics of these cells are hardly detectable and we suppose that they undergo cell death. Other canals pass down deeper into the lower hypertrophic zone. The upper segment of these canals is composed of capillaries, mesenchymal cells, and macrophage-like cells. Precursors of osteoblasts are adjacent to the canals. The lower segment of communicating canals is composed of bone matrix or osteoid, which contains type I collagen fibrils and cells having the typical subcellular features of osteoblasts. No vessels are found in these segments. Immunohistochemistry shows that the matrix of the canals labels positively for type I collagen. In addition, staining with sirius red demonstrates that bone matrix is formed in these parts. We assume that the osteoblast-like cells of the lower segments of communicating canals originate either from mesenchymal cells or even from hypertrophic chondrocytes. Our immunohistochemical data also reveal that vascular endothelial growth factor (VEGF) and the corresponding receptor VEGFR2/Flk1 (VEGF receptor 2/Flk1) are localized in cartilage canals of the reserve zone, the proliferative zone, and the hypertrophic zone. The receptor is found in the endothelial cells of the vessels. Furthermore, VEGF is present in hypertrophic chondrocytes. The results of our study suggest that cartilage canals penetrate actively into the cartilage anlage and that bone is formed in the lower segments of the communicating canals where no vessels are detectable.
Anat Rec A Discov Mol Cell Evol Biol 2004 Jul
PMID:Cartilage canals in the chicken embryo are involved in the process of endochondral bone formation within the epiphyseal growth plate. 1522 11

The study examined the expression of matrix metalloproteinases (MMPs), type I collagen and osteocalcin during bone healing in a rat calvarial experimental defect model. Twelve-week-old male Wistar rats were used. A full-thickness standardized trephine defect was made in the parietal bone, with the rat under anesthesia. RNA was extracted from tissue that filled the original bone defect on days 1 and 3 and in weeks 1, 2, 3, 5, 8, 10, 12, 18, and 24 and processed for quantitative analysis of expression of type I collagen, osteocalcin and matrix metalloproteinases (MMPs) 2, 8, and 13 by using real-time polymerase chain reaction. Alternatively, the rats were fixed by perfusion through the aorta and resected calvaria were processed for in situ hybridization for these molecules. The expression of type I collagen, osteocalcin and MMPs 2 and 13 increased toward week 2 and decreased thereafter, whereas the expression of MMP 8 was the highest on day 1. The mRNA transcripts of type I collagen and osteocalcin were localized in osteoblasts and osteocytes, some of which expressed MMPs 2, 8, and 13. Osteoblasts and osteocytes may play a role in the remodeling of extracellular matrices with MMPs during healing of a defect in bone.
Anat Rec (Hoboken) 2008 Aug
PMID:Quantitative analysis and localization of mRNA transcripts of type I collagen, osteocalcin, MMP 2, MMP 8, and MMP 13 during bone healing in a rat calvarial experimental defect model. 1861 87


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