Review article: anti‐fibrotic agents for the treatment of Crohn’s disease – lessons learnt from other diseases

Szabó, Hajnalka; Fiorino, Gionata; Spinelli, Antonino; Rovida, Serena; Repici, Alessandro; Malesci, Alberto; Danese, Silvio

doi:10.1111/j.1365-2036.2009.04171.x

Cited by 29 publications

(28 citation statements)

References 121 publications

(246 reference statements)

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“…TGFβ represents one of the key molecules involved in stricture formation, promoting the phenotypic change of fibroblasts into myofibroblasts through the activation of the small mother against decapentaplegic SMAD proteins (Szabo et al, 2010). Bowel wall thickening appears macroscopically in the late stage of inflammation, although experimental evidence suggests that the underlying mechanisms begin at the very early stage of inflammation (Rieder et al, 2012).…”

Section: Inflammatory Bowel Disease Models In Intestinal Fibrosis Resmentioning

confidence: 99%

“…Bowel wall thickening appears macroscopically in the late stage of inflammation, although experimental evidence suggests that the underlying mechanisms begin at the very early stage of inflammation (Rieder et al, 2012). However, transforming growth factor β (TGFβ) targeting still represents a challenging task as it also exerts anti-inflammatory activity and mediates several cellular communication pathways (Szabo et al, 2010).…”

Section: Inflammatory Bowel Disease Models In Intestinal Fibrosis Resmentioning

confidence: 99%

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Animal models of chemically induced intestinal inflammation: Predictivity and ethical issues

Dothel

Vasina

Barbara

et al. 2013

Pharmacology & Therapeutics

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Section: Inflammatory Bowel Disease Models In Intestinal Fibrosis Resmentioning

confidence: 99%

Section: Inflammatory Bowel Disease Models In Intestinal Fibrosis Resmentioning

confidence: 99%

Animal models of chemically induced intestinal inflammation: Predictivity and ethical issues

Dothel

Vasina

Barbara

et al. 2013

Pharmacology & Therapeutics

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“…In this instance, BMP-7 peptide binds to the extracellular 34 However, BMP-7 growth factor does not prevent 35 Bleomycin-induced adult human/mouse lung and skin specific fibrosis. The mechanism of BMP-7 opposing TGF-b1-mediated collagen induction in mouse pulmonary myofibroblasts was known to be mediated through Id2 protein 36 and other regulatory proteins in complex signaling pathways that are beyond the scope of this study.…”

Section: Discussionmentioning

confidence: 99%

“…This is important as complete knockdown of TGF-b1 can have deleterious effects on normal cellular functions. 34 The expression of Phospho-Smad 1/5/8 (Supplementary Fig. 2A) indicates that BMP-7 signaling is activated intracellularly, accumulating primarily in the cytosol.…”

Section: Discussionmentioning

confidence: 99%

Anti‐fibrosis effect of BMP‐7 peptide functionalization on cobalt chromium alloy

Tan

Poh

Cai

et al. 2013

Journal Orthopaedic Research

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Orthopedic metallic prosthetic implants are commonly made of cobalt chromium (CoCr) alloys. However, such metal-based implants are susceptible to fibrous capsule formation on the implant surface after implantation. At the bone-implant interface, this capsule can prevent implant integration, resulting in loosening and failure. Minimizing the development of such a capsule on the CoCr surface would improve direct bone-implant bonding leading to long-term implant functionality. We evaluated the anti-fibrosis effect of bone morphogenic protein-7 (BMP-7) peptide covalently bonded to CoCr alloy. This peptide, a biomimetic derivation of the knuckle epitope of BMP-7, was conjugated at the N-terminus with a cysteine amino acid. X-ray photoelectron spectroscopy (XPS) and probe binding assay were used to evaluate different stages of grafting and surface functionalization using polydopamine coating. Cellular functions were studied using fibroblast attachment, cell proliferation, and MTT assays. Fibroblasts were grown on functionalized and pristine CoCr substrates, and the efficacy of BMP-7 peptide on anti-fibrosis was analyzed via gene expression and protein expression of fibrosis markers ACTA2, Collagen 1A1, and fibronectin. The peptide functionalized substrates showed significant reduction of fibrosis markers expression after 1 week of incubation compared to controls. BMP-7 signaling pathway activation was shown by the presence of phosphorylation of Smad1/5/8. These findings may contribute to the improvement of CoCr implants in orthopedic surgery applications.

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“…Another review in this series addresses the promise of targeting myofibroblasts for stem cell therapy. All these approaches are being attempted in the management of liver fibrosis (discussed in another chapter of this series) or fibrosis associated with other chronic inflammatory disorders (36,51,56) and should be applied to the intestine. Finally, we need to take into account not only how, but also when to intervene in the evolving profibrogenic process.…”

Section: Clinical and Therapeutic Considerationsmentioning

confidence: 98%

Themes in fibrosis and gastrointestinal inflammation

Fiocchi

Lund

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Wound healing is an appropriate response to inflammation and tissue injury in the gastrointestinal tract. If wound healing responses are excessive, perpetuated, or prolonged, they lead to fibrosis, distortion of tissue architecture, and loss of function. This introductory editorial and the minireviews or reviews in this themes series highlight the diversity in severity and location of fibrosis in response to gastrointestinal inflammation. The multiplicity of cellular and molecular mediators and new players, including stem cells or extracellular matrix-producing cells derived from nonmesenchymal cell types, is reviewed. Comparisons of inflammation-induced fibrosis across organ systems and the need for integrated and systems-based molecular approaches, new imaging modalities, well-characterized animal models, cell culture models, and improved diagnostic or predictive markers are reviewed. To date, intestinal fibrosis has received much less attention than inflammation in terms of defining mechanisms and underlying causes. This themes series aims to illustrate the importance of research in this area in gastrointestinal health and disease.

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Review article: anti‐fibrotic agents for the treatment of Crohn’s disease – lessons learnt from other diseases

Abstract: SUMMARY BackgroundThe current therapies for Crohn's disease (CD) are mainly focused on blockade of inflammation. Fibrosis remains one of the major complications of CD often leading to surgery, affecting patients' quality-of-life.

Cited by 29 publications

References 121 publications

Animal models of chemically induced intestinal inflammation: Predictivity and ethical issues

Animal models of chemically induced intestinal inflammation: Predictivity and ethical issues

Anti‐fibrosis effect of BMP‐7 peptide functionalization on cobalt chromium alloy

Themes in fibrosis and gastrointestinal inflammation

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