ArticlePloS one2015
Celiac Disease Histopathology Recapitulates Hedgehog Downregulation, Consistent with Wound Healing Processes Activation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Transcriptomic analysis of intestine following administration of a transglutaminase 2 inhibitor to prevent gluten-induced intestinal damage in celiac disease.Nature immunology · 2024Trial
- Genome-Wide Transcriptomic Analysis of Intestinal Mucosa in Celiac Disease Patients on a Gluten-Free Diet and Postgluten Challenge.Cellular and molecular gastroenterology and hepatology · 2021Trial
- A foundational approach to culture and analyze malnourished organoids.Gut microbes · 2023Article
- Morbid Obesity in Women Is Associated with an Altered Intestinal Expression of Genes Related to Cancer Risk and Immune, Defensive, and Antimicrobial Response.Biomedicines · 2022Article
- Effect of Gluten-Free Diet on Gut Microbiota Composition in Patients with Celiac Disease and Non-Celiac Gluten/Wheat Sensitivity.Nutrients · 2020Review
- Small-bowel carcinomas associated with celiac disease: transcriptomic profiling shows predominance of microsatellite instability-immune and mesenchymal subtypes.Virchows Archiv : an international journal of pathology · 2020Article
- An Exploratory Gene Expression Study of the Intestinal Mucosa of Patients with Non-Celiac Wheat Sensitivity.International journal of molecular sciences · 2020Article
- Role of IL-24 in the mucosal remodeling of children with coeliac disease.Journal of translational medicine · 2020Article
- Celiac disease: a comprehensive current review.BMC medicine · 2019Review
- Breaking Down Barriers: How Understanding Celiac Disease Pathogenesis Informed the Development of Novel Treatments.Digestive diseases and sciences · 2019Review
- Human gut derived-organoids provide model to study gluten response and effects of microbiota-derived molecules in celiac disease.Scientific reports · 2019Article
- RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis.PloS one · 2019Article
- Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: The Current Knowledge.Cancers · 2018Review
- Human Fetal-Derived Enterospheres Provide Insights on Intestinal Development and a Novel Model to Study Necrotizing Enterocolitis (NEC).Cellular and molecular gastroenterology and hepatology · 2018Article
- Exploring the villus.Gastroenterology and hepatology from bed to bench · 2018Review
- Small bowel carcinomas in celiac or Crohn's disease: distinctive histophenotypic, molecular and histogenetic patterns.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundIn 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
findingsImmunohistochemistry, 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.
conclusionsOur 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.
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