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10.1371/journal.pone.0144634 http://scihub22266oqcxt.onion/10.1371/journal.pone.0144634 C4674131!4674131 !26649570     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26649570 &cmd=llinks): Failed to open stream: HTTP request failed! 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Celiac Disease Histopathology Recapitulates Hedgehog Downregulation, Consistent with Wound Healing Processes Activation |pdf=|usr=}}{{26649570 }} gab.com Text Celiac Disease Histopathology Recapitulates Hedgehog Downregulation, Consistent with Wound Healing Processes Activation JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=26649570 #FOAvip BACKGROUND: In celiac disease (CD), intestinal epithelium damage occurs secondary to an immune insult and is characterized by blunting of the villi and crypt hyperplasia. Similarities between Hedgehog (Hh)/BMP4 downregulation, as reported in a mouse model, and CD histopathology, suggest mechanistic involvement of Hh/BMP4/WNT pathways in proliferation and differentiation of immature epithelial cells in the context of human intestinal homeostasis and regeneration after damage. Herein we examined the nature of intestinal crypt hyperplasia and involvement of Hh/BMP4 in CD histopathology. METHODS AND FINDINGS: Immunohistochemistry, qPCR and in situ hybridization were used to study a cohort of 24 healthy controls (HC) and 24 patients with diagnosed acute celiac disease (A-CD) intestinal biopsies. In A-CD we observed an increase in cells positive for Leucin-rich repeat-containing G protein-coupled receptor 5 (LGR5), an epithelial stem cell specific marker and expansion of WNT responding compartment. Further, we observed alteration in number and distribution of mesenchymal cells, predicted to be part of the intestinal stem cells niche. At the molecular level we found downregulation of indian hedgehog (IHH) and other components of the Hh pathway, but we did not observe a concurrent downregulation of BMP4. However, we observed upregulation of BMPs antagonists, gremlin 1 and gremlin 2. CONCLUSIONS: Our data suggest that acute CD histopathology partially recapitulates the phenotype reported in Hh knockdown models. Specifically, Hh/BMP4 paradigm appears to be decoupled in CD, as the expansion of the immature cell population does not occur consequent to downregulation of BMP4. Instead, we provide evidence that upregulation of BMP antagonists play a key role in intestinal crypt hyperplasia. This study sheds light on the molecular mechanisms underlying CD histopathology and the limitations in the use of mouse models for celiac disease. Twit Text FOAVip Celiac Disease Histopathology Recapitulates Hedgehog Downregulation, Consistent with Wound Healing Processes Activation ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=26649570 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26649570 #FOAvip English Wikipedia <ref>{{Cite pmid|26649570 }}</ref> Celiac Disease Histopathology Recapitulates Hedgehog Downregulation, Consistent with Wound Healing Processes Activation #MMPMID26649570 Senger S ; Sapone A ; Fiorentino MR ; Mazzarella G ; Lauwers GY ; Fasano A PLoS One 2015[]; 10 (12 ): e0144634 PMID26649570 show ga BACKGROUND: In celiac disease (CD), intestinal epithelium damage occurs secondary to an immune insult and is characterized by blunting of the villi and crypt hyperplasia. Similarities between Hedgehog (Hh)/BMP4 downregulation, as reported in a mouse model, and CD histopathology, suggest mechanistic involvement of Hh/BMP4/WNT pathways in proliferation and differentiation of immature epithelial cells in the context of human intestinal homeostasis and regeneration after damage. Herein we examined the nature of intestinal crypt hyperplasia and involvement of Hh/BMP4 in CD histopathology. METHODS AND FINDINGS: Immunohistochemistry, qPCR and in situ hybridization were used to study a cohort of 24 healthy controls (HC) and 24 patients with diagnosed acute celiac disease (A-CD) intestinal biopsies. In A-CD we observed an increase in cells positive for Leucin-rich repeat-containing G protein-coupled receptor 5 (LGR5), an epithelial stem cell specific marker and expansion of WNT responding compartment. Further, we observed alteration in number and distribution of mesenchymal cells, predicted to be part of the intestinal stem cells niche. At the molecular level we found downregulation of indian hedgehog (IHH) and other components of the Hh pathway, but we did not observe a concurrent downregulation of BMP4. However, we observed upregulation of BMPs antagonists, gremlin 1 and gremlin 2. CONCLUSIONS: Our data suggest that acute CD histopathology partially recapitulates the phenotype reported in Hh knockdown models. Specifically, Hh/BMP4 paradigm appears to be decoupled in CD, as the expansion of the immature cell population does not occur consequent to downregulation of BMP4. Instead, we provide evidence that upregulation of BMP antagonists play a key role in intestinal crypt hyperplasia. This study sheds light on the molecular mechanisms underlying CD histopathology and the limitations in the use of mouse models for celiac disease. |*Down-Regulation [MESH] |Animals [MESH] |Bone Morphogenetic Protein 4/*metabolism [MESH] |Bone Morphogenetic Proteins/metabolism [MESH] |Case-Control Studies [MESH] |Celiac Disease/metabolism/*pathology [MESH] |Cell Differentiation [MESH] |Cell Proliferation [MESH] |Cytokines [MESH] |Epithelial Cells/metabolism [MESH] |Hedgehog Proteins/*metabolism [MESH] |Humans [MESH] |Intercellular Signaling Peptides and Proteins/metabolism [MESH] |Intestinal Mucosa/metabolism [MESH] |Intestine, Small/metabolism [MESH] |Mice [MESH] |Regeneration/physiology [MESH] |Stem Cells/metabolism [MESH] |Wnt Signaling Pathway [MESH]Celiac Disease Histopathology Recapitulates Hedgehog Downregulation, C(epmc).pdf DeepDyve Pubget Overpricing