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At least 865 records · Page 48Linked to original sources
PubMed2002

Thrombin activation of S-phase reentry by cultured pigmented epithelial cells of adult newt iris.

Following local injury or tissue removal, regeneration in urodele amphibians appears to be dependent on cell cycle reentry and dedifferentiation of postmitotic, terminally differentiated cells in the remaining tissues. Regeneration of the lens of the eye occurs by the dedifferentiation of pigmented epithelial cells (PEC) of the iris and their subsequent transdifferentiation into lens cells. A key question is how cell cycle reentry is regulated. Here we demonstrate that thrombin activates S-phase reentry of newt PEC in vitro. Based on these findings, and on previous experiments showing that newt skeletal myotubes reenter the cell cycle following thrombin stimulation, we suggest that thrombin is a critical signal for initiation of vertebrate regeneration.

Animals↗
PubMed1998

Regulation of homeobox-containing genes during lens regeneration.

In this study, the expression of homeobox-containing genes was evaluated after lentectomy in the newt, which is competent for lens regeneration, and in the axolotl which is not. Such a comparison was designed to offer insights about possible regulation due to regenerative abilities. Six homeobox-containing genes were examined: NvHox A4, NvHox B1, NvHox 7, NvHox X, Nvmsx-1 and Xbr1. For all genes examined, it was found that soon after lentectomy in the newt there was a general down-regulation in the retina. This down-regulation varied among the Hox genes with NvHox 7 and NvHox B1 being virtually absent in the initial stages; their expression was re-established to the original levels after the reappearance of lens. The expression patterns, for NvHox 7 and NvHox B1 were the same when the lens was removed and then displaced. However, in axolotl, down-regulation was not observed. These data suggest that the observed regulation is related to the process of lens regeneration and provide the first molecular evidence that lens regeneration could be dependent on retina and underline the importance of this tissue in lens regeneration. Such patterns link expression of homeobox-containing genes and lens regeneration and can be now used to understand the underlying mechanisms of lens regeneration and transdifferentiation.

Ambystoma mexicanum↗
PubMed2002

Inhibitory effects of salmosin, a disintegrin, on posterior capsular opacification in vitro and in vivo.

The proliferation, migration and transdifferentiation of the remaining lens epithelial cells (LECs) after cataract surgery are a major cause of posterior capsular opacification (PCO). It has previously been reported that salmosin, a novel disintegrin, significantly inhibits solid tumor growth in mice by perturbation of tumor-specific angiogenesis via blocking alpha v beta 3 integrin expressed on vascular endothelial cells. In this study, the inhibitory function of salmosin in PCO was investigated and was found that salmosin inhibits the attachment of bovine LECs and rabbit lens cells (N/N1003A) to extracellular matrix-coated plates. The anti-adhesive activity of salmosin was approximately 1000 times higher than that of synthetic Arg-Gly-Asp peptide. In addition, the cell proliferation and migration of bovine LECs and N/N1003A were strongly inhibited by salmosin, whereas the proliferation of corneal endothelial cells was less affected. LEC migration and proliferation were also decreased by salmosin treatment in rabbit eyes without any toxic effect in the cornea, iris and retina. In this study, salmosin was shown to specifically inhibit LEC migration and proliferation in an animal model. Therefore, the authors suggest that further investigation may show salmosin to be a good candidate for inhibiting PCO development.

Animals↗
PubMedDate not supplied

Connective tissue growth factor: what's in a name?

Connective tissue growth factor (CTGF) is a member of the recently described CCN gene family which contains CTGF itself, cyr61, nov, elm1, Cop1, and WISP-3. CTGF is transcriptionally activated by several factors although its stimulation by transforming growth factor beta (TGF-beta) has attracted considerable attention. CTGF acts to promote fibroblast proliferation, migration, adhesion, and extracellular matrix formation, and its overproduction is proposed to play a major role in pathways that lead to fibrosis, especially those that are TGF-beta-dependent. This includes fibrosis of major organs, fibroproliferative diseases, and scarring. CTGF also appears to play a role in the extracellular matrix remodeling that occurs in normal physiological processes such as embryogenesis, implantation, and wound healing. However, recent advances have shown that CTGF is involved in diverse autocrine or paracrine actions in several other cell types such as vascular endothelial cells, epithelial cells, neuronal cells, vascular smooth muscle cells, and cells of supportive skeletal tissues. Moreover, in some circumstances CTGF has negative effects on cell growth in that it can be antimitotic and apoptotic. In light of these discoveries, CTGF has been implicated in a diverse variety of processes that include neovascularization, transdifferentiation, neuronal scarring, atherosclerosis, cartilage differentiation, and endochondral ossification. CTGF has thus emerged as a potential important effector molecule in both physiological and pathological processes and has provided a new target for therapeutic intervention in fibrotic diseases.

Amino Acid Sequence↗
PubMed1998

Alterations in the growth factor signal transduction pathways and modulators of the cell cycle in endocervical cells from macaques exposed to TCDD.

After more than a year had elapsed since a single oral exposure to 2 and 4 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg, there was an apparent dose-related increased incidence of significant endocervical squamous metaplasia in a group of cynomolgus macaques (Scott et al., 1998). In the present experiments we investigated the mechanisms by which chemicals like TCDD could induce epithelial cell transdifferentiation in the primate endocervix. One focus of investigation was epidermal growth factor receptor (EGFR) and the key cytosolic signaling kinases, c-Src and protein tyrosine kinase (PTK), whose responses to TCDD are well characterized. A second focus was the distal kinase Erk2 that transduces the cytosolic signal into a nuclear signal, and which in combination with nuclear casein kinase II (CKII), can lead to activation of p53. Finally, we studied three key target proteins of activated p53 (wafl/p21, Cdc2 p34, and Cdk4), whose modulation could produce cell cycle effects. The studies were carried out using primary cell cultures prepared from endocervical epithelium recovered at necropsy from TCDD-treated (2 and 4 microgram TCDD/kg) and untreated macaques. There was a significant decrease in EGFR binding activity in cells from TCDD-treated animals as compared to controls. A marked increase in the protein amount of H-Ras and a significant increase in the activity of c-Src kinase, PTK, and Erk2 were found in cells from TCDD-treated animals. A significant decrease in the activity of CKII and in the protein amount of p53, wafl/p21, and Cdc2 p34 was found. On the other hand, a substantial increase in the protein amount of Cdk4 and DNA binding activity of AP-1 was found in cells from TCDD-treated animals. In vitro experiments using primary cultures of endocervical cells from untreated macaques revealed that these cells have AhR, and that c-Src protein is functionally attached to the AhR and is specifically activated upon ligand binding as judged by the following criteria. (1) A structure-activity relationship study with TCDD and three dioxin congeners revealed a rank order for their potency in activation of AhR-associated c-Src kinase from cervical cells which was identical to that of previously determined toxicity indices. (2) TCDD-induced, AhR-associated c-Src kinase activity was abolished when an AhR immunoprecipitate from cervical cells was preincubated with alpha-naphthoflavone (AhR blocker) or geldanamycin (Src kinase inhibitor) prior to the addition of TCDD. (3) The analysis of the AhR complex showed three proteins of molecular weights of 100 (AhR), 90, and 60 kDa. (4) The same protein with molecular weight 60 kDa was found when the immunoprecipitate with anti AhR-antibody was analyzed by SDS-PAGE, then transferred into nitrocellulose membrane followed by immunobloting the membrane with anti c-Src-antibody. Our data suggest that TCDD induced pathology in endocervical cells through changes in growth factor receptor signaling, other cytosolic signaling proteins, tumor suppressor proteins, and cell cycle proteins.

Animals↗
PubMed2003

In vitro transformation of monocytes and dendritic cells into endothelial like cells.

Our in vitro data indicate that peripheral blood monocytes or monocyte-derived immature dendritic cells under appropriate culture conditions transdifferentiate into endothelial-like cells (ELC), which are characterized by the expression of endothelial markers and the formation of tube-like structures. Dependent on the culture conditions a mixed macrophage/endothelial or an endothelial phenotype could be induced. A similar pattern of development could be seen in CD14+ monocyte-derived ELC and ELC grown from CD34+ precursor cells or from dendritic cells generated from CD34+ cells. These in vitro data suggest that monocytes are precursors of different subgroups of endothelial cells and that the formation of endothelial cells from CD34+ progenitor cells follows a similar pathway possibly via the monocyte and/or the immature dendritic cell.

Animals↗
PubMed2006

Future and applications of cloning.

The birth of viable offspring from somatic cell nuclear transfer (SCNT) in mammals caused a major re-examination of the understanding of the commitment of cells to specific tissue lineages during differentiation. The questions of whether cells undergo dedifferentiation or transdifferentiation during the development of offspring and how these changes are controlled is a source of ongoing debate that is yet to be resolved. Irrespective of the outcome of this debate, it is clear that cloning using SCNT has a place and purpose in the future of research and animal breeding. The future uses of SCNT could include the production of transgenic mice, the production of transgenic livestock and assisting with the re-establishment of endangered species. Human medicine also would benefit from future use of SCNT because it would allow the production of patient-specific embryonic stem cells.

Animals↗
PubMed2004

Amphibian regeneration and stem cells.

Larval and adult urodeles and anuran tadpoles readily regenerate their limbs via a process of histolysis and dedifferentiation of mature cells local to the amputation surface that accumulate under the wound epithelium as a blastema of stem cells. These stem cells require growth and trophic factors from the apical epidermal cap (AEC) and the nerves that re-innervate the blastema for their survival and proliferation. Members of the fibroblast growth factor (FGF) family synthesized by both AEC and nerves, and glial growth factor, substance P, and transferrin of nerves are suspected survival and proliferation factors. Stem cells derived from fibroblasts and muscle cells can transdifferentiate into other cell types during regeneration. The regeneration blastema is a self-organizing system based on positional information inherited from parent limb cells. Retinoids, which act through nuclear receptors, have been used in conjunction with assays for cell adhesivity to show that positional identity of blastema cells is encoded in the cell surface. These molecules are involved in the cell-cell signaling network that re-establishes the original structural pattern of the limb. Other systems of interest that regenerate by histolysis and dedifferentiation of pigmented epithelial cells are the neural retina and lens. Members of the FGF family are also important to the regeneration of these structures. The mechanism of amphibian regeneration by dedifferentiation is of importance to the development of a regenerative medicine, since understanding this mechanism may offer insights into how we might chemically induce the regeneration of mammalian tissues.

Amphibians↗
PubMed2004

Existence of reserve quiescent stem cells in adults, from amphibians to humans.

Several theories have been proposed to explain the phenomenon of tissue restoration in amphibians and higher order animals. These theories include dedifferentiation of damaged tissues, transdifferentiation of lineage-committed stem cells, and activation of quiescent stem cells. Young and colleagues demonstrated that connective tissues throughout the body contain multiple populations of quiescent lineage-committed progenitor stem cells and lineage-uncommitted pluripotent stem cells. Subsequent cloning and cell sorting studies identified quiescent lineage-uncommitted pluripotent mesenchymal stem cells, capable of forming any mesodermal cell type, and pluripotent epiblastic-like stem cells, capable of forming any somatic cell type. Based on their studies, they propose at least 11 categories of quiescent reserve stem cells resident within postnatal animals, including humans. These categories are pluripotent epiblastic-like stem cells, pluripotent ectodermal stem cells, pluripotent epidermal stem cells, pluripotent neuronal stem cells, pluripotent neural crest stem cells, pluripotent mesenchymal (mesodermal) stem cells, pluripotent endodermal stem cells, multipotent progenitor stem cells, tripotent progenitor stem cells, bipotent progenitor stem cells, and unipotent progenitor stem cells. Thus, activation of quiescent reserve stem cells, i.e., lineage-committed progenitor stem cells and lineage-uncommitted pluripotent stem cells, resident within the connective tissues could provide for the continual maintenance and repair of the postnatal organism after birth.

Adult↗
PubMed1981

The problem of automation in animal development: confrontation of the concept of cell sociology with biochemical data.

The principles of automation in animal development, as previously inferred from the concept of Cell Sociology do not fit in well with the current concept of sequential genet derepression. A more adequate explanation for those principles has been found in the literature dealing with the biochemical aspects of differentiation. Since oocytes and embryonic cells contain a greater variety of mRNAs than differentiated cells, as well as many tissue-specific (luxury) substances, it is concluded that the diversification of tissues consists of a progressive selection of specific metabolic strategies, mediated by cell-to-cell contacts, from a broad range of pre-existing strategies. For each tissue, prior to its final determination, one luxury metabolic strategy is progressively intensified and becomes dominant. The others are either suppressed or maintained as latent metabolic strategies. The latter may on occasion become dominant again (transdifferentiation). These phenomena require a theory which considers gene regulation as the activation of otherwise repressed genes by specific activator RNAs. The high (apparently maximal) transcriptional activity on the lampbrush chromosomes may represent the synthesis of all the kinds of activator RNAs which are required for the reactivation of the genes during early development. A general conception is propounded of the automatism and programming of animal development, as inferred from the confrontation of these ideas with the concept of Cell Sociology.

Animals↗
PubMed1993

Presence of chondroid bone on rat mandibular condylar cartilage. An immunohistochemical study.

Immunohistochemical techniques were used to examine the locations of type I and type II collagens in the the most anterior and the posterosuperior regions of the mandibular condylar cartilages of young and adult rats. Large ovoid and polygonal cells, which were morphologically different from any of the neighboring cells, e.g., mature or hypertrophied chondrocytes, osteoblasts, or fibroblasts, were observed at the most anterior margin of the young and adult condylar cartilages. In the extracellular matrix (ECM) of this area, an eosinophilic staining pattern similar to that in bone matrix was observed, while the peripheral ECM showed basophilic staining and very weak reactivity to Alcian blue. Immunohistochemical examination showed that the ECM was stained heavily and diffusely for type I collagen, while a staining for type II collagen was faint and limited to the peripheral ECM. Two different staining patterns for type II collagen could be recognized in the ECM: one pattern revealed a very faint and diffuse reaction while the other showed a wak rim-like reaction. These staining patterns were markedly different from those in the cartilaginous cell layer in the posterosuperior area of the condylar secondary cartilage, which showed faint staining for type I collagen and a much more intense staining for type II collagen. These observations reveal the presence of chondroid bone, a tissue intermediate between bone and cartilage tissues, in the mandibular condylar cartilage, and suggest the possibility of osteogenic transdifferentiation of mature chondrocytes.

Animals↗
PubMedDate not supplied

Glycoantigen expression is regulated both temporally and spatially during development in the cellular slime molds Dictyostelium discoideum and D. mucoroides.

Six monoclonal antibodies were isolated which react with common antigens shared by multiple glycoconjugate species in the cellular slime mold Dictyostelium discoideum. Based on competition of antibody binding by glycopeptides and simple sugars, and inhibition of antibody binding by antigen pretreatment with Na periodate, it is argued that at least five of the six antibodies recognize epitopes which contain carbohydrate. These epitopes are consequently referred to as glycoantigens (GAs). Three of the GAs are expressed during growth and throughout the developmental cycle, but are eventually enriched in prestalk and stalk cells. The remaining three are expressed only during and/or after aggregation and are exclusively expressed or highly enriched in prespore cells and spores. These conclusions are derived from Western blot immunoanalysis of purified cell types, immunofluorescence, and EM immunocytochemistry. The two GAs found only in prespore cells appear to be exclusively enclosed within prespore vesicles. The third GA of this type, which is only enriched in prespore cells compared to prestalk cells, is also found in other vesicle types as well as on the cell surface. Two of the GAs enriched in prestalk cells are initially found in all cells of the slug. They are undetectable in spores and prominent in stalk cells. The third GA, though found in the interiors of both prestalk and prespore cells, is enriched on the cell surface of prestalk cells. The chief characteristics of expression of four of these GAs are conserved in the related species D. mucoroides. This species is characterized by continuous transdifferentiation of prespore cells into prestalk cells. This shows that the prespore cells maintain specific mechanisms for turning over their cell type specific GAs and that prestalk cells express a specific mechanism for inducing at least one of their cell-type specific GAs. These observations identify specific carbohydrate structures (as GAs) whose synthesis, subsequent localization and turnover are developmentally regulated. The exclusive association of two GAs with prespore vesicles identifies these GAs as markers for this organelle and raises questions regarding the functional significance of this association. The restricted cell surface localization of the other four GAs, together with data from cell adhesion studies, suggest the possibility of a potential role for these GAs in intercellular recognition leading to cell sorting.

Antibodies, Monoclonal↗
PubMed1992

Cell specific DNA-labelling in the repairing blood-brain barrier of the insect Periplaneta americana.

This study uses a recently developed technique for preserving the ultrastructure of cells in the insect CNS during immunohistochemical processing for 5-bromo-2-deoxyuridine incorporation into newly synthesised DNA. The results allow us to identify the proliferating cell classes in the regenerating blood-brain barrier. High resistance barrier cells do not label with the antibody but sheath cells clearly do. Intermediate cell types appearing during repair are identified. It is hypothesised that these cells generate matrix molecules for neural lamella repair and may represent transitional forms as invasive blood cells transdifferentiate into functional sheath cells.

Animals↗
PubMed1997

Cell types of secondary cataract: an immunohistochemical analysis with antibodies to cytoskeletal elements and macrophages.

BACKGROUND: The study was carried out to identify cell types of secondary cataract after extracapsular cataract extraction and implantation of an intraocular lens. METHODS: Twenty-five formalin-fixed, paraffin-embedded pseudophakic human eyes with secondary cataract, obtained at autopsy, were studied and compared to a specimen from an anterior subcapsular cataract with a panel of six monoclonal antibodies (MAbs, to vimentin, cytokeratin (CK) 8 and 18, desmin, alpha-smooth muscle actin, and the CD68 epitope of macrophages by the avidin-biotinylated peroxidase complex (ABC) method. RESULTS: MAb Vim 3B4 to vimentin immunolabeled spindle-shaped cells in 16 of 17 central plaques of secondary cataract as well as cells in all 16 Soemmering's ring cataracts. Spindle-shaped cells reacted with MAb CAM 5.2 to CK 8 in 13 of 18 eyes, but only one specimen was labeled with MAb CY-90 to CK 18. No immunoreaction was seen with MAb D33 to desmin, whereas MAb 1A4 to alpha-smooth muscle actin immunolabeled spindle-shaped cells in 15 of 18 plaques of secondary cataract. Macrophages were seen with MAb PG-M1 in 13 of 19 secondary cataracts. In the anterior subcapsular cataract, spindle-shaped cells under a wrinkled but otherwise intact capsule reacted with MAb Vim 3B4 to vimentin, MAb CAM 5.2 to CK 8, and MAb 1A4 to alpha-smooth muscle actin. CONCLUSION: Spindle-shaped cells in secondary and anterior subcapsular cataracts react with antibodies to vimentin, CK 8 and alpha-smooth muscle actin, suggesting them to be metaplastic epithelial cells that derive from the lens epithelium. alpha-Smooth muscle actin persists in them at least 10 years postoperatively, but CK 8 starts to disappear after 3 years. Macrophages are one possible modulator of this transdifferentiation.

Aged↗
PubMed1997

Iris pigment epithelium transplantation.

BACKGROUND: Iris pigment epithelium (IPE) cells and retinal pigment epithelium (RPE) cells possess the same embryonic origin. It is also known that the pigmented epithelial cells in the eye have a high transdifferentiation potential. In this study we transplanted IPE cells into the subretinal space of albino Royal College of Surgeons (RCS) rats and evaluated their influence on the degeneration of the photoreceptors. METHODS: IPE cells of Long Evans rats were isolated and pure cultures were obtained. The isolated cells were transplanted into the subretinal space of RCS rats. Light microscopic and morphometric analysis were carried out. RESULTS: The IPE transplants survived in the subretinal space and attached themselves to the Bruch's membrane. The transplanted cells were able to delay the degeneration of the photoreceptors for up to 3 months. CONCLUSION: These results suggest that IPE cells could be successfully transplanted and survive in the subretinal space. In the transplanted eyes the photoreceptors were preserved for a period of 3 months. Further studies are needed to explore the capability of IPE cells to assume the main functions of RPE cells in the subretinal space and their potential in the therapy of selective degenerative diseases of the retina.

Animals↗
PubMed1994

Mouse pancreatic acinar/ductular tissue gives rise to epithelial cultures that are morphologically, biochemically, and functionally indistinguishable from interlobular duct cell cultures.

Most of the pancreatic exocrine epithelium consists of acinar and intralobular duct (ductular) cells, with the balance consisting of interlobular and main duct cells. Fragments of mouse acinar/ductular epithelium can be isolated by partial digestion with collagenase and purified by Ficoll density gradient centrifugation. We investigated whether previously developed culture conditions used for duct epithelium would result in the selective survival and proliferation of ductular cells from the acinar/ductular fragments. The fragments were cultured on nitrocellulose filters coated with extracellular matrix. After 2 to 4 wk the filters were covered with proliferating cells resembling parallel cultures of duct epithelium by the following criteria: protein/DNA ratio, light and electron microscopic appearance, the presence of duct markers (carbonic anhydrase [CA] activity, CA II mRNA, the cystic fibrosis transmembrane conductance regulator), the near absence of acinar cell markers (amylase and chymotrypsin), a similar polypeptide profile after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the presence of spontaneous and secretin-stimulated electrogenic ion transport. Both duct and ductular epithelia formed fluid-filled cysts in collagen gels and both could be subcultured. We conclude that acinar/ductular tissue gives rise to ductular cells in culture by some combination of acinar cell death and/or transdifferentiation to a ductular phenotype, accompanied by proliferation of these cells and preexisting ductular cells. These cultures may be used to investigate the properties of this part of the pancreatic duct system, from which most of the pancreatic juice water and electrolytes probably originates.

Amylases↗
PubMed2005

Temporal expression of Notch in preterm rat lungs exposed to hyperoxia.

To explore the mechanism of Notch in hyperoxia-induced preterm rat lung injury, 2-days-old preterm SD rats were randomized into control and hyperoxia group (FiO2 > or = 0.85). On day 1, 7, 14 and 21, 8 rat pups of each time point were used to assess histopathological changes of lung with HE staining and to evaluate the expression of Notch1 and Notch3 with immunohistochemistry. Notch1, Notch3, Aquaprin5 (AQP5) and surfactant protein C (SP-C) mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). The results showed that the lung injury in the hyperoxia group was characterized by retarded lung alveolization and differentiation of alveolar epithelial type II cells (AEC II). Positive staining of Notch1 in hyperoxia group was weaker than controls at every time point (except for day 7), while positive staining of Notch3 was much stronger (P < 0.05, P < 0.01). Notch1, Notch3 mRNA level showed similar change as protein level. AQP5, SP-C mRNA decreased significantly as compared with that of the controls (P < 0.01). We are led to conclude that hyperoxia results in abnormal expression of Notch, which is likely to contribute to the pathogenesis of lung injury through regulating proliferation and transdifferentiation of alveolar epithelial cells.

Aerobiosis↗
PubMed2005

Expression of TGF-beta2 mRNA and PCNA, FN protein in lens epithelial cells in age-related nuclear and cortex cataract.

By using RT-PCR and immunohistochemistry, the expressions of transforming growth factor beta2 (TGF-beta2) mRNA, proliferating cell nuclear antigen (PCNA) and fibronection (FN) protein in lens epithelial cells (LECs) of age-related nuclear and cortex cataract were detected and compared. The results of RT-PCR revealed that the expression of TGF-beta2 mRNA was higher in cortex cataract than in nuclear cataract. Immunohistochemistry demonstrated that the expression of PCNA protein was lower and the expression of FN protein was higher in cortex cataract than in nuclear cataract. It was suggested that TGF-beta2, PCNA and FN might take important parts in the process of age-related cataract. Cortex cataract was related to the transdifferentiation of LECs, and nuclear cataract to the proliferation of LECs.

Aged↗