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- He, Liqun, et al.
(författare)
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The glomerular transcriptome and a predicted protein-protein interaction network
- 2008
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 19:2, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the molecular composition of the kidney glomerulus, we performed a meta-analysis of available glomerular transcriptional profiles made from mouse and man using five different methodologies. We generated a combined catalogue of glomerulus-enriched genes that emerged from these different sources and then used this to construct a predicted protein-protein interaction network in the glomerulus (GlomNet). The combined glomerulus-enriched gene catalogue provides the most comprehensive picture of the molecular composition of the glomerulus currently available, and GlomNet contributes an integrative systems biology approach to the understanding of glomerular signaling networks that operate during development, function, and disease.
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| 4. |
- Sun, Ying, 1955
(författare)
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Neural control of colonic epithelial transport, motility and permeability in vivo. An experimental study in anaesthetized rats
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colonic dysfunction may result in diarrhoea, abdominal pain or constipation, andinflammatory bowel disease, bile acid malabsorption and particularly irritable bowelsyndrome are very common disorders. The role of the enteric nervous system (ENS) inthese diseases is largely unknown. Therefore, the purpose of this study was to investigatethe effects of enteric nerves on colonic epithelial transport, motility and permeabilityunder normal and bile acid exposed condition.The studies of colonic motility, transmural potential difference (PD), net fluid transportand permeability were carried out on the isolated proximal and distal rat colon with intactblood supply and innervation, mainly in vivo. 3H-mannitol and 14C-urea wereadministered i.v. as clearance probes. 4 mM decoxycholic acid (DCA) was put into thelumen to induce chemical irritation of the surface epithelium. The effects of the nerveblockers atropine, hexamethonium, lidocaine (applied onto the serosal surface) and thenitric oxide inhibitor Nw-nitro-L-arginine (L-NNA) were studied under control conditionsand during mucosal bile acid exposure.Muscarinic receptor blockade with atropine inhibited motor activity, had no significanteffect on net fluid transport and inhibited the bile acid induced increase in small solutepermeability. Nicotinic receptor blockade with hexamethonium abolished motor activity,enhanced electrically silent absorption in proximal colon, inhibited electrogenic secretionin distal colon and inhibited the bile acid induced permeability increase. Serosal lidocaineinduced colonic contractions, dissociated the normal linkage between contractions andsecretion, and inhibited the bile acid induced permeability increase in proximal colon.NO synthesis blockade with L-NNA potentiated the bile acid induced permeabilityincrease in distal colon.The data suggest that the ENS regulates not only colonic motility and secretion but alsocolonic permeability. The neural control of the colonic mucosa seems to be differentlyorganized from that of the small intestine. Instead of activating secretomotor neurons,chemical stimulation with bile acids leads to a largely neurally mediated increase incolonic permeability, a response that is in turn inhibited by nitric oxide. These resultssuggest that enteric nerves may play a pathophysiological role in the inflamed colonicmucosa. Pharmacological intervention with the neurally mediated permeability-regulatingsystem may be a new target for treatment of colonic secretomotor disorders.
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| 5. |
- Takemoto, Minoru, et al.
(författare)
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Large-scale identification of genes implicated in kidney glomerulus development and function.
- 2006
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Ingår i: The EMBO journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 25:5, s. 1160-74
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Tidskriftsartikel (refereegranskat)abstract
- To advance our understanding of development, function and diseases in the kidney glomerulus, we have established and large-scale sequenced cDNA libraries from mouse glomeruli at different stages of development, resulting in a catalogue of 6053 different genes. The glomerular cDNA clones were arrayed and hybridized against a series of labeled targets from isolated glomeruli, non-glomerular kidney tissue, FACS-sorted podocytes and brain capillaries, which identified over 300 glomerular cell-enriched transcripts, some of which were further sublocalized to podocytes, mesangial cells and juxtaglomerular cells by in situ hybridization. For the earliest podocyte marker identified, Foxc2, knockout mice were used to analyze the role of this protein during glomerular development. We show that Foxc2 controls the expression of a distinct set of podocyte genes involved in podocyte differentiation and glomerular basement membrane maturation. The primary podocyte defects also cause abnormal differentiation and organization of the glomerular vascular cells. We surmise that studies on the other novel glomerulus-enriched transcripts identified in this study will provide new insight into glomerular development and pathomechanisms of disease.
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