Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.14.11.2 (prolyl hydroxylase)
1,814 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The origin of the stromal, stellate and multinucleate cells in oral giant cell fibroma is unclear. Sixteen giant cell fibromas were stained immunocytochemically for keratin (MNF 116), vimentin, S-100 protein, neurofilaments, glial fibrillary acidic protein, alpha-smooth muscle actin, desmin, CD31 (PECAM-1), CD68, Factor XIIIa and prolyl 4-hydroxylase (5B5). In all cases positive staining was found with vimentin and prolyl 4-hydroxylase, indicating a functional fibroblast phenotype. Reactivity for Factor XIIIa was seen in two cases and in only one was a small number of giant cells stained, suggesting that the majority of oral giant cell fibromas are unrelated to the histologically similar fibrous papule of the nose or facial angiofibroma.
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PMID:Phenotypic characterisation of stellate and giant cells in giant cell fibroma by immunocytochemistry. 752 65

Cells differing widely in tissue distribution, immunophenotype and ultrastructure have been described as myofibroblasts. The definition of the myofibroblast was analysed as applied to normal tissues, with original observations on Wharton's jelly stromal cells as an example. Stromal cells in Wharton's jelly were studied by conventional histology, immunohistochemistry, and electron microscopy. The normal architecture of the cord was confirmed by light microscopy. Stromal cells and the smooth-muscle cells of the umbilical vessels were positive for vimentin, desmin and alpha-smooth muscle actin, while only the stromal cells were positive for prolyl 4-hydroxylase. Electron microscopy revealed variable but sometimes only moderate amounts of rough endoplasmic reticulum, bundles of smooth-muscle type filaments with focal densities, a large Golgi apparatus with collagen secretion granules, lipid and glycogen. There was no convincing evidence for either lamina or fibronexus junctions. The nature of the stromal cell was discussed in the light of these findings. It was concluded that a myofibroblastic designation was inappropriate and that these cells had phenotypic similarities to vascular smooth muscle cells. The possibility is proposed that most examples of spindle cells cited in the literature as being myofibroblasts and seen in normal tissues not subjected to trauma or showing pathology may be pericytic or smooth-muscle in nature.
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PMID:Defining the myofibroblast: normal tissues, with special reference to the stromal cells of Wharton's jelly in human umbilical cord. 808 99

Rat pancreatic periacinar fibroblastoid cells (PFCs) appear to be involved in intralobular fibrosis and acinar cell regeneration. We isolated pancreatic acini of the rat, cultured the fibroblastoid cells, and characterized the cells morphologically and immunohistochemically. Isolated acini were seeded on culture dishes, and spindle-shaped cells migrated and proliferated. On Electronmicroscopic examination, microfilament bundles were seen, and the intracellular localization of vimentin, alpha-smooth muscle actin, and non-muscle myosin was identified immunohistochemically. These findings strongly suggest that the cells were myofibroblast-like. The PFCs were also demonstrated, immunohistochemically, to contain prolyl hydroxylase, type-I procollagen, type-III procollagen, type-IV collagen, fibronectin, and laminin. Stimulation by transforming growth factor beta 1 (TGF beta 1) increased intracellular immunoreactive prolyl hydroxylase and collagen synthesis in the PFCs. These findings indicate that PFCs proliferate in culture as myofibroblast-like cells and synthesize extracellular matrix components. It is possible that PFCs are involved in intralobular fibrosis in response to stimulation with TGF beta 1.
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PMID:Morphological identification of and collagen synthesis by periacinar fibroblastoid cells cultured from isolated rat pancreatic acini. 884 79

Fibroblast-like cells in the periacinar region may play an important role in periacinar fibrosis. In the present study, we isolated and cultured periacinar fibroblast-like cells (PFCs) derived from human pancreatic acini and examined the characteristics of human PFCs morphologically and immunocytochemically. Immunocytochemical study of human PFCs showed that they were positively stained with antibodies against type I collagen/procollagen, type III collagen/procollagen, fibronectin, prolyl hydroxylase beta sub-unit, type IV collagen, laminin, alpha-smooth muscle actin, vimentin, and nonmuscle myosin. Electron microscopic study showed that human PFCs contained a number of microfilaments, forming dense bodies in the cytoplasm. These results indicated that human PFCs possess characteristics of myofibroblasts. Expression of alpha-smooth muscle actin, a marker of the myofibroblast-like phenotype, was increased with time in culture and was enhanced by treatment with transforming growth factor (TGF)-beta 1. Collagen synthesis in human PFCs was stimulated by TGF-beta 1 and the proliferation of human PFCs was stimulated by platelet-derived growth factor. These findings suggest that PFCs from human pancreas seem to be involved in periacinar fibrosis.
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PMID:Morphological and immunocytochemical identification of periacinar fibroblast-like cells derived from human pancreatic acini. 916 84

Lens capsules become fibrotic after the extraction of a cataract. To understand this phenomenon, we evaluated the immunolocalization of prolyl 4-hydroxylase (an enzyme involved in procollagen hydroxylation), and extracellular matrix components and cytoskeletal components in a normal human lens capsule and in others with intraocular lenses. Lens capsules containing intraocular lenses were removed from a patient with proliferative vitreoretinopathy and three with proliferative diabetic retinopathy during vitreous surgery. Two circular sections of the anterior capsules with lens epithelial cells were obtained by anterior capsulotomy during cataract surgery. In addition, a lens capsular bag was obtained immediately after phacoemulsification. The lens capsules were processed for light microscopic immunohistochemical detection of the alpha and beta subunits of prolyl 4-hydroxylase, extracellular matrix components (including collagen types, laminin and cellular fibronectin) or cytoskeletal components (such as cytokeratin, vimentin and alpha-smooth muscle actin). Monolayer lens epithelial cells were seen on the inner surface of the normal anterior capsules. Each intraocular lens was found to be fixed in the capsular bag. Light microscopic immunohistochemistry showed that these proliferating cells expressed vimentin and alpha-smooth muscle actin; in contrast, quiescent lens epithelial cells did not stain for alpha-smooth muscle actin. Marked immunostaining for subunits of prolyl 4-hydroxylase was detected in lens epithelial cells proliferating on the capsules, while no or only faint prolyl 4-hydroxylase immunoreactivity was detected in quiescent lens epithelial cells immediately after phacoemulsification. Collagen types I, III and VI and cellular fibronectin were observed diffusely in accumulated connective tissue on a capsule with an intraocular lens. Type IV collagen immunoreactivity was seen both in the capsules and in the connective tissue accumulation on the capsules. Collagen V and laminin were detected in association with cellular proliferation. Collagen VII and VIII and laminin 5 were not seen. We concluded that during wound healing of the lens capsule after cataract extraction, the lens epithelial cells that proliferate on the inner surface of the capsule transform it into a myofibroblastic phenotype, expressing prolyl 4-hydroxylase and alpha-smooth muscle actin. These proliferating cells are involved in the production of collagen on the lens capsule. This results in a postoperative fibrotic process and contraction of the lens capsule.
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PMID:Immunolocalization of prolyl 4-hydroxylase subunits, alpha-smooth muscle actin, and extracellular matrix components in human lens capsules with lens implants. 953 56

Fetal placental vessels develop and adapt in order to supply the fetus with nutrients. Immunostaining by antibodies against blood clotting factors, cell-cell and cell-matrix adhesion molecules, intermediate and contractile filaments, matrix components and enzymes give an overall view useful in assessing cell differentiation in placental villi. Endothelial cells stained positively for thrombomodulin, von Willebrand factor, CD34, CD31, cadherin-5, phalloidin and alpha 3-integrin. Trophoblastic cells were positive for cytokeratin, alpha 5 and alpha V integrins, L-prolyl hydroxylase and phalloidin. Myocytes from the media of stem villi exhibited positive vimentin, desmin, alpha-sm-actin and sm-myosin reactions but were CD26 negative. Myofibroblasts were vimentin, desmin, CD26, alpha-sm-actin and sm-myosin positive. Perivascular cells of intermediate and terminal villi were alpha-sm-actin, sm-myosin and anti-high molecular weight melanoma associated antigen (HMWMAA) positive. Trophoblastic and endothelial basement membranes were collagen IV positive. The most specific endothelial markers were cadherin-5, observed only at paracellular clefts, and von Willebrand factor. For perivascular cells, alpha-sm-actin, sm-myosin and HMWMAA provided a specific labeling. Differences in labeling intensity were noted along the cross section of the villous tree (vimentin, desmin, actin, myosin inward gradient). A continuity in the contractile function along the vessel length was indicated by alpha-sm-actin and sm-myosin positive cells, contrasting with the decreased von Willebrand reaction intensity. These data are discussed in relation to cell function and compared to cell culture results.
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PMID:Immunostaining of vascular, perivascular cells and stromal components in human placental villi. 1009 44

Astrocytes express four types of Cl(-) or anion channels, but Ca(2+)-activated Cl(-) (Cl(Ca)) channels have not been described. We studied Cl(-) channels in a morphologically distinct subpopulation ( approximately 5% of cells) of small (10-12 micro m, 11.8 +/- 0.6 pF), phase-dark, GFAP-positive native reactive astrocytes (NRAs) freshly isolated from injured adult rat brains. Their resting potential, -57.1 +/- 4.0 mV, polarized to -72.7 +/- 4.5 mV with BAPTA-AM, an intracellular Ca(2+) chelator, and depolarized to -30.7 +/- 6.1 mV with thapsigargin, which mobilizes Ca(2+) from intracellular stores. With nystatin-perforated patch clamp, thapsigargin activated a current that reversed near the Cl(-) reversal potential, which was blocked by Cl(-) channel blockers, 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and Zn(2+), by I(-) (10 mM), and by chlorotoxin (EC(50) = 47 nM). With conventional whole-cell clamp, NPPB- and Zn(2+)-sensitive currents became larger with increasing [Ca(2+)](i) (10, 150, 300 nM). Single-channel recordings of inside-out patches confirmed Ca(2+) sensitivity of the channel and showed open-state conductances of 40, 80, 130, and 180 pS, and outside-out patches confirmed sensitivity to chlorotoxin. In primary culture, small phase-dark NRAs developed into small GFAP-positive bipolar cells with chlorotoxin-sensitive Cl(Ca) channels. Imaging with biotinylated chlorotoxin confirmed the presence of label in GFAP-positive cells from regions of brain injury, but not from uninjured brain. Chlorotoxin-tagged cells isolated by flow cytometry and cultured up to two passages exhibit positive labeling for GFAP and vimentin, but not for prolyl 4-hydroxylase (fibroblast), A2B5 (O2A progenitor), or OX-42 (microglia). Expression of a novel chlorotoxin-sensitive Cl(Ca) channel in a morphologically distinct subpopulation of NRAs distinguishes these cells as a new subtype of reactive astrocyte.
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PMID:Chlorotoxin-sensitive Ca2+-activated Cl- channel in type R2 reactive astrocytes from adult rat brain. 1273 Sep 53

In the present study, we examined the expression and the localization of apamin-sensitive small conductance Ca(2+)-activated K(+) channels (SK channels) in the mouse intestine. SK3-immunoreactivity (IR) was detected in both ileum and colon. Double staining experiments showed that SK3-IR was colocalized with prolyl 4-hydroxylase (PH(alpha))-IR, but not with c-Kit-IR which are markers of fibroblast cells and the interstitial cells of Cajal (ICC), respectively. Although SK3-IR was colocalized with vimentin-IR, which is another marker of ICC, the reactivity of SK3-immunopositive cells was weaker than that of ICC. The SK3-immunopositive cells were similarly present in the intestine of c-Kit mutant mice (W/W(V)), in which ICC were absent, and its wild-type mice. The immuno-electron microscopic analysis indicated that SK3 was localized in the cells that had some similar morphological features to ICC, but obviously different from ICC. The SK3-immunopositive cells had gap junctions with the smooth muscle cells. The gap junctions were smaller than those between ICC and smooth muscle cells. These results indicate expression of SK3 in fibroblast-like cells, but not in ICC, and suggest participation of the cells in the intestinal motility.
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PMID:Localization of Ca2+-activated K+ channel, SK3, in fibroblast-like cells forming gap junctions with smooth muscle cells in the mouse small intestine. 1283 53

Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate along different pathways including chondrogenic, osteogenic and adipogenic lineages. MSCs with a fibroblast-like morphology have been identified in human fetal lung. However, their frequency and characterization in human adult lung have not been yet evaluated. Therefore, we analyzed the mesenchymal phenotype and differentiation ability of cultured human adult bronchial fibroblast-like cells (Br) in comparison with those of mesenchymal cell progenitors isolated from fetal lung (ICIG7) and adult bone marrow (BM212) tissues. Surface immunophenotyping by flow cytometry revealed a similar expression pattern of antigens characteristic of marrow-derived MSCs, including CD34 (-), CD45 (-), CD90/Thy-1 (+), CD73/SH3, SH4 (+), CD105/SH2 (+) and CD166/ALCAM (+) in Br, ICIG7 and BM212 cells. There was one exception, STRO-1 antigen, which was only weakly expressed in Br cells. Analysis of cytoskeleton and matrix composition by immunostaining showed that lung and marrow-derived cells homogeneously expressed vimentin and nestin proteins in intermediate filaments while they were all devoid of epithelial cytokeratins. Additionally, alpha-smooth muscle actin was also present in microfilaments of a low number of cells. All cell types predominantly produced collagen and fibronectin extracellular matrix as evidenced by staining with the monoclonal antibodies to collagen prolyl 4-hydroxylase and fibronectin isoforms containing the extradomain (ED)-A together with ED-B in ICIG7 cells. Br cells similarly to fetal lung and marrow fibroblasts were able to differentiate along the three adipogenic, osteogenic and chondrogenic mesenchymal pathways when cultured under appropriate inducible conditions. Altogether, these data indicate that MSCs are present in human adult lung. They may be actively involved in lung tissue repair under physiological and pathological circumstances.
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PMID:Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. 1592 48

Oxidative stress has been implicated in the pathogenesis of neuronal degenerative diseases. It is also widely known that oxidative stress induces mitogen-activated protein kinase (MAPK) signaling cascades. In this study, we used proteomic analysis to investigate the role of the MAPK pathway in oxidative stress-induced neuronal cell death. The results demonstrated that several proteins, including eukaryotic translation elongation factor 2 (eEF2) and enolase I, showed a differential expression pattern during the neuronal cell death process, and this was MAPK pathway dependent. Several chaperone and cytoskeletal proteins including heat shock protein 70, calreticulin, vimentin, prolyl 4-hydroxylase beta polypeptide, and transgelin 2 were up-or down-regulated, despite their expressions not depending on the MAPK pathway. These findings strongly suggest that the expressions of proteins which play protective roles are independent of the MAPK pathway. On the other hand, eEF2 and enolase I may be the downstream targets of the MAPK pathway.
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PMID:A proteomic analysis of the effect of MAPK pathway activation on L-glutamate-induced neuronal cell death. 1712 46


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