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| 2. |
- Brisslert, Mikael, 1974, et al.
(författare)
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Intra-peritoneal sRAGE treatment induces alterations in cellular distribution of CD19(+), CD3 (+) and Mac-1 (+) cells in lymphoid organs and peritoneal cavity.
- 2013
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 351:1, s. 139-48
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Tidskriftsartikel (refereegranskat)abstract
- Receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that binds a variety of pro-inflammatory ligands. Its soluble form, sRAGE, can compete for ligand binding and thereby have an anti-inflammatory effect. We have recently reported that sRAGE also exerts pro-inflammatory and chemotactic properties suggesting a dual role for sRAGE in immune modulation. Our present aim was to analyse the immunomodulatory properties of sRAGE in vivo with respect to acquired immunity. Naive mice were treated intra-peritoneally with sRAGE and cells from peritoneal lavage, spleens and bone marrow were examined. Mice treated with sRAGE displayed an increased leucocyte count in the peritoneal cavity, enlarged spleens and increased cellularity compared with vehicle-treated animals. Furthermore, sRAGE-treated mice had a significantly increased frequency and number of CD19(+) B cells in spleen and a reduced frequency of CD19(+) B cells in bone marrow compared with controls. Functionally, splenocytes from sRAGE-treated mice showed elevated IgG production and up to a four-fold increased IgM secretion compared with control animals and produced significantly higher levels of interleukin-10, interferon-γ and interleukin-6 in response to lipopolysaccharide stimulation. Our results suggest that sRAGE has immunomodulatory properties, since intra-peritoneal administration of sRAGE into healthy mice leads to rearrangements in cellular composition in the bone marrow and spleen. Moreover, the administration of sRAGE directs B cells into the spleen and towards differentiation. Our novel findings indicate that sRAGE exerts an effect on the cells of adaptive immunity.
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| 3. |
- Carlsson, Mikael A., et al.
(författare)
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Distribution of short neuropeptide F and its receptor in neuronal circuits related to feeding in larval Drosophila
- 2013
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 353:3, s. 511-523
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Tidskriftsartikel (refereegranskat)abstract
- Four forms of short neuropeptide F (sNPF1-4), derived from the gene snpf, have been identified in Drosophila and are known to act on a single G-protein-coupled receptor (sNPFR). Several functions have been suggested for sNPFs in Drosophila, including the regulation of feeding and growth in larvae, the control of insulin signalling and the modulation of neuronal circuits in adult flies. Furthermore, sNPF has been shown to act as a nutritional state-dependent neuromodulator in the olfactory system. The role of sNPF in the larval nervous system is less well known. To analyse sites of action of sNPF in the larva, we mapped the distribution of sNPF- and sNPFR-expressing neurons. In particular, we studied circuits associated with chemosensory inputs and systems involved in the regulation of feeding, including neurosecretory cell systems and the hypocerebral ganglion. We employed a combination of immunocytochemistry and enhancer trap and promoter Gal4 lines to drive green fluorescent protein. We found a good match between the distribution of the receptor and its ligand. However, several differences between the larval and adult systems were observed. Thus, neither sNPF nor its receptor was found in the olfactory (or other sensory) systems in the larva and cells producing insulin-like peptides did not co-express sNPFR, as opposed to results from adults. Moreover, sNPF was expressed in a subpopulation of Hugin cells (second-order gustatory neurons) only in adult flies. We propose that the differences in sNPF signalling between the developmental stages is explained by differences in their feeding behaviour.
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| 4. |
- Degerman, Eva, et al.
(författare)
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Expression of insulin signalling components in the sensory epithelium of the human saccule.
- 2013
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 1432-0878 .- 0302-766X. ; 352:3, s. 469-478
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have demonstrated a link between diabetes and the dysfunction of the inner ear. Few studies, however, have reported the signalling mechanisms involved in metabolic control in human inner ear cells. Knowledge of the expression and role of the insulin receptor and downstream signalling components in the inner ear is sparce. Our immunohistochemistry approach has shown that the insulin receptor, insulin receptor substrate 1 (IRS1), protein kinase B (PKB) and insulin-sensitive glucose transporter (GLUT4) are expressed in the sensory epithelium of the human saccule, which also exhibits expression of a calcium-sensitive cAMP/cGMP phosphodiesterase 1C (PDE1C) and the vasopressin type 2 receptor. IRS1 and PDE1C are selectively expressed in sensory epithelial hair cells, whereas the other components are expressed in sensory epithelial supporting cells or in both cell types, as judged from co-expression or non-co-expression with glial fibrillary acidic protein, a marker for supporting cells. Furthermore, IRS1 appears to be localized in association with sensory nerves, whereas GLUT4 is expressed in the peri-nuclear area of stromal cells, as is the case for aquaporin 2. Thus, the insulin receptor, insulin signalling components and selected cAMP signalling components are expressed in the human saccule. In addition to well-known mechanisms of diabetes complications, such as neuropathy and vascular lesions, the expression of these proteins in the saccule could have a role in the observed link between diabetes and balance/hearing disorders.
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| 5. |
- Durbeej-Hjalt, Madeleine
(författare)
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Laminins.
- 2010
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 1432-0878 .- 0302-766X. ; 339, s. 259-268
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Tidskriftsartikel (refereegranskat)abstract
- Laminins are cell adhesion molecules that comprise a family of glycoproteins found predominantly in basement membranes, which are the thin sheets of extracellular matrix that underlie epithelial and endothelial cells and surround muscle cells, Schwann cells, and fat cells. Many laminins self-assemble to form networks that remain in close association with cells through interactions with cell surface receptors. Laminins are vital for many physiological functions. They are essential for early embryonic development and organogenesis and have crucial functions in several tissues including muscle, nerve, skin, kidney, lung, and the vasculature. A great wealth of data on laminins is available, and an in-depth description is not attempted here. In this review, I will instead provide a snapshot of laminin structure, tissue distribution, and interactions with other matrix molecules and receptors and briefly describe laminin mutations in mice and humans. Several illuminating and timely reviews are cited that can be consulted for references to original articles and more detailed information concerning laminins.
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| 6. |
- Eckhard, Andreas, et al.
(författare)
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Co-localisation of Kir4.1 and AQP4 in rat and human cochleae reveals a gap in water channel expression at the transduction sites of endocochlear K+ recycling routes
- 2012
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 350:1, s. 27-43
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Tidskriftsartikel (refereegranskat)abstract
- Sensory transduction in the cochlea depends on perilymphatic-endolymphatic potassium (K+) recycling. It has been suggested that the epithelial supporting cells (SCs) of the cochlear duct may form the intracellular K+ recycling pathway. Thus, they must be endowed with molecular mechanisms that facilitate K+ uptake and release, along with concomitant osmotically driven water movements. As yet, no molecules have been described that would allow for volume-equilibrated transepithelial K+ fluxes across the SCs. This study describes the subcellular co-localisation of the Kir4.1 K+ channel (Kir4.1) and the aquaporin-4 water channel (AQP4) in SCs, on the basis of immunohistochemical double-labelling experiments in rat and human cochleae. The results of this study reveal the expression of Kir4.1 in the basal or basolateral membranes of the SCs in the sensory domain of the organ of Corti that are adjacent to hair cells and in the non-sensory domains of the inner and outer sulci that abut large extracellular fluid spaces. The SCs of the inner sulcus (interdental cells, inner sulcus cells) and the outer sulcus (Hensen’s cells, outer sulcus cells) display the co-localisation of Kir4.1 and AQP4 expression. However, the SCs in the sensory domain of the organ of Corti reveal a gap in the expression of AQP4. The outer pillar cell is devoid of both Kir4.1 and AQP4. The subcellular co-localisation of Kir4.1 and AQP4 in the SCs of the cochlea described in this study resembles that of the astroglia of the central nervous system and the glial Mueller cells in the retina.
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| 7. |
- Einarsdottir, Ingibjörg, 1951, et al.
(författare)
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Occurrence of ghrelin-producing cells, the ghrelin receptor and Na+,K+-ATPase in tissues of Atlantic halibut
- 2011
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Ingår i: Cell and Tissue Resarch. - 0302-766X. ; 344:3, s. 481-498
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin is a pituitary growth hormone (GH)-secretagogue that also has metabolic, reproductive, proliferative, immunological and brain functions in mammals. Far less is known about its role in fish. We have therefore performed an immunohistochemical determination of its tissue distribution in the developing Atlantic halibut (Hippoglossus hippoglossus) to gain insights into its potential function. Ghrelin immunoreactivity was detected in first-feeding halibut larvae in the skin, urinary bladder, gastrointestinal (GI) tract and olfactory lobe of the brain. In subsequent stages up to metamorphosis, ghrelin immunoreactivity declined in the skin and became evident in the gills. When the stomach developed, ghrelin immunoreactivity declined throughout the GI tract with the exception of the stomach, which exhibited an intense signal. Immunoreactive ghrelin cells were also present in the olfactory lobe, nerve and epithelium and in occasional cells of the buccal cavity and oesophagus. Ghrelin immunoreactivity had an overlapping distribution with that for Na(+),K(+)-ATPase, colocalisation also being observed in some ionocytes of the gill. The co-expression of ghrelin and the GH-secretagogue receptor in the same tissue indicates that ghrelin can exert both endocrine and paracrine actions in the developing halibut. The presence of immunoreactive ghrelin in several osmoregulatory tissues, the GI tract and sensory tissue provides strong evidence that ghrelin has multiple functions during development and also suggests targets for future investigations.
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| 8. |
- Fong, Gloria, et al.
(författare)
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Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway
- 2013
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Ingår i: Cell and Tissue Research. - : Springer-Verlag New York. - 0302-766X .- 1432-0878. ; 351:3, s. 465-475
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Tidskriftsartikel (refereegranskat)abstract
- Studies of human patellar and Achilles tendons have shown that primary tendon fibroblasts (tenocytes) not only have the capacity to produce acetylcholine (ACh) but also express muscarinic ACh receptors (mAChRs) through which ACh can exert its effects. In patients with tendinopathy (chronic tendon pain) with tendinosis, the tendon tissue is characterised by hypercellularity and angiogenesis, both of which might be influenced by ACh. In this study, we have tested the hypothesis that ACh increases the proliferation rate of tenocytes through mAChR stimulation and have examined whether this mechanism operates via the extracellular activation of the epidermal growth factor receptor (EGFR), as shown in other fibroblastic cells. By use of primary human tendon cell cultures, we identified cells expressing vimentin, tenomodulin and scleraxis and found that these cells also contained enzymes related to ACh synthesis and release (choline acetyltransferase and vesicular acetylcholine transporter). The cells furthermore expressed mAChRs of several subtypes. Exogenously administered ACh stimulated proliferation and increased the viability of tenocytes in vitro. When the cells were exposed to atropine (an mAChR antagonist) or the EGFR inhibitor AG1478, the proliferative effect of ACh decreased. Western blot revealed increased phosphorylation, after ACh stimulation, for both EGFR and the extracellular-signal-regulated kinases 1 and 2. Given that tenocytes have been shown to produce ACh and express mAChRs, this study provides evidence of a possible autocrine loop that might contribute to the hypercellularity seen in tendinosis tendon tissue.
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| 9. |
- Hagström, Christina, et al.
(författare)
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Glial cells revealed by GFAP immunoreactivity in fish gut.
- 2010
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Ingår i: Cell and tissue research. - : Springer Science and Business Media LLC. - 1432-0878 .- 0302-766X. ; 341:1, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- Glial fibrillary acidic protein (GFAP) is a commonly used marker to identify enteric glia in the mammalian gut. Little is however known about enteric glia in other vertebrates. The aim of the present study was to examine the distribution of GFAP immunoreactivity in adult and developing fish. In adult shorthorn sculpin (Myoxocephalus scorpius) and zebrafish (Danio rerio), GFAP immunoreactivity was seen in the myenteric plexus in all regions of the gut. Co-staining for the neuronal markers Hu C/D and acetylated tubulin showed that GFAP immunoreactivity was not associated with nerves. GFAP immunoreactivity was predominantly seen in processes with few glial cell bodies being demonstrated in adult fish. GFAP immunoreactivity was also found in the gut in larval zebrafish from 3 days post-fertilisation, i.e. at approximately the same time that differentiated enteric nerve cells first occur. Immunoreactivity was most prominent in areas with no or a low density of Hu-immunoreactive nerve cell bodies, indicating that the developing glia follows a different pattern from that of enteric neurons. The results suggest that GFAP can be used as a marker for enteric glia in fish, as in birds and mammals. The distribution of GFAP immunoreactivity implies that enteric glia are widespread in the fish gastrointestinal tract. Glia and neurons diverge early during development of the gastrointestinal tract.
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| 10. |
- Heldin, Carl-Henrik, 1952-, et al.
(författare)
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Role of Smads in TGFβ signaling
- 2012
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 347:1, s. 21-36
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Forskningsöversikt (refereegranskat)abstract
- Transforming growth factor-β (TGFβ) is the prototype for a large family of pleiotropic factors that signal via heterotetrameric complexes of type I and type II serine/threonine kinase receptors. Important intracellular mediators of TGFβ signaling are members of the Smad family. Smad2 and 3 are activated by C-terminal receptor-mediated phosphorylation, whereafter they form complexes with Smad4 and are translocated to the nucleus where they, in cooperation with other transcription factors, co-activators and co-repressors, regulate the transcription of specific genes. Smads have key roles in exerting TGFβ-induced programs leading to cell growth arrest and epithelial-mesenchymal transition. The activity and stability of Smad molecules are carefully regulated by a plethora of post-translational modifications, including phosphorylation, ubiquitination, sumoylation, acetylation and poly(ADP)-ribosylation. The Smad function has been shown to be perturbed in certain diseases such as cancer.
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