ArticleExperimental and molecular pathology2012
CARD-024, a vitamin D analog, attenuates the pro-fibrotic response to substrate stiffness in colonic myofibroblasts.
Article in Experimental and molecular pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The Role of Vitamin D Supplementation on Airway Remodeling in Asthma: A Systematic Review.Nutrients · 2023Pooled it
- Hypertrophic Scars: Are Vitamins and Inflammatory Biomarkers Related with the Pathophysiology of Wound Healing?Obesity surgery · 2017Trial
- The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Inflammation-fibrosis interplay in inflammatory bowel disease: mechanisms, progression, and therapeutic strategies.Frontiers in pharmacology · 2025Review
- Joint Detection of Serum Vitamin D, Body Mass Index, and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn's Disease.Current medical science · 2023Article
- The Role of Vitamins in the Pathogenesis of Asthma.International journal of molecular sciences · 2023Review
- Gut Microbiota, Macrophages and Diet: An Intriguing New Triangle in Intestinal Fibrosis.Microorganisms · 2022Review
- Effect of ABT-263 on Intestinal Fibrosis in Human Myofibroblasts, Human Intestinal Organoids, and the Mouse Salmonella typhimurium Model.Inflammatory bowel diseases · 2022Article
- A broad look into the future of systemic sclerosis.Therapeutic advances in musculoskeletal disease · 2022Review
- Diet in Intestinal Fibrosis: A Double-Edged Sword.Nutrients · 2021Review
- AXL Is a Potential Target for the Treatment of Intestinal Fibrosis.Inflammatory bowel diseases · 2021Article
- Shared and distinct mechanisms of fibrosis.Nature reviews. Rheumatology · 2019Review
- Measurement of Fibrosis in Crohn's Disease Strictures with Imaging and Blood Biomarkers to Inform Clinical Decisions.Digestive diseases (Basel, Switzerland) · 2017Review
- Nutritional Aspects of Gastrointestinal Wound Healing.Advances in wound care · 2016Review
- Intestinal organoids: a model of intestinal fibrosis for evaluating anti-fibrotic drugs.Experimental and molecular pathology · 2015Article
- Elimination of vitamin D receptor in vascular endothelial cells alters vascular function.Hypertension (Dallas, Tex. : 1979) · 2014Article
- Link between vitamin D and airway remodeling.Journal of asthma and allergy · 2014Review
- Novel Rho/MRTF/SRF inhibitors block matrix-stiffness and TGF-β-induced fibrogenesis in human colonic myofibroblasts.Inflammatory bowel diseases · 2014Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Intestinal fibrosis is one of the major complications of Crohn's disease (CD) for which there are no effective pharmacological therapies. Vitamin D deficiency is common in CD, though it is not known whether this is a contributing factor to fibrosis, or simply a consequence of the disease itself. In CD, fibrosis is mediated mainly by activated intestinal myofibroblasts during remodeling of extracellular matrix in response to wound healing. We investigated the effects of CARD-024 (1-alpha-hydroxyvitamin D5), a vitamin D analog with minimal hypercalcemic effects, on the pro-fibrotic response of intestinal myofibroblasts to two fibrogenic stimuli: TGFβ stimulation and culture on a physiologically stiff matrix. TGFβ stimulated a fibrogenic phenotype in Ccd-18co colonic myofibroblasts, characterized by an increase in actin stress fibers and mature focal adhesions, and increased αSMA protein expression, while CARD-024 repressed αSMA protein expression in a dose-dependent manner. Culture of colonic myofibroblasts on physiological high stiffness substrates induced morphological changes with increased actin stress fibers and focal adhesion staining, induction of αSMA protein expression, FAK phosphorylation, induction of fibrogenic genes, and repression of COX-2 and IL-1β. CARD-024 treatment repressed the stiffness-induced morphological features including stellate cell morphology and the maturation of focal adhesions. CARD-024 repressed the stiffness-mediated induction of αSMA protein expression, FAK phosphorylation, and MLCK and ET-1 gene expression. In addition, CARD-024 partially stimulated members of the COX-2/IL-1β inflammatory pathway. In summary, CARD-024 attenuated the pro-fibrotic response of colonic myofibroblasts to high matrix stiffness, suggesting that vitamin D analogs such as CARD-024 may ameliorate intestinal fibrosis.
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Registered trials
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