Extracellular Matrix Fragments of the Basement Membrane and the Interstitial Matrix Are Serological Markers of Intestinal Tissue Remodeling and Disease Activity in Dextran Sulfate Sodium Colitis

Lindholm, Majken; Manon‐Jensen, Tina; Madsen, Gunvor Iben; Krag, Aleksander; Karsdal, Morten A.; Kjeldsen, Jens; Mortensen, Joachim Høg

doi:10.1007/s10620-019-05676-6

Cited by 28 publications

(33 citation statements)

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“…7 Therefore, proteins related to the intestinal epithelium for assessing intestinal permeability/epithelial integrity and intestinal tissue homeostasis may be used to evaluate the disease burden. 1,11,[13][14][15][25][26][27] The antibody in the PRO-C23 ELISA only recognised the C-terminus sequence of the ectodomain of type 23 collagen and had no cross-reaction with the C-terminus of type XIII and XXV collagen, which have similar sequences. This data confirmed the specificity of the antibody.…”

Section: Discussionmentioning

confidence: 99%

“…Adapted from Karsdal et al 27 inflamed intestinal tissue, [7][8][9][10] and increased ECM remodeling was highly affected in both UC and CD, including remodelling of the basement membrane which was also related to epithelial cells driven by increased protease activity. [11][12][13][14][15][16][17][18][19][20][21] Based on this background it was likely that type 23 collagen was also affected by the ECM remodelling in UC and CD. Type 23 collagen was found to be related to cell adhesion and metastasis in vitro.…”

Section: Introductionmentioning

confidence: 99%

“…UNITED EUROPEAN GASTROENTEROLOGY JOURNAL intestinal permeability/epithelial integrity and intestinal tissue homeostasis may be used to evaluate the disease burden. 1,11,[13][14][15][25][26][27] The There are several limitations to this study. First, we cannot exclude that PRO-C23 may be released from other tissues than the intestines; however, the DSS colitis models confirm that PRO-C23 is a product of the intestinal mucosa remodelling, suggesting that PRO-C23 at least is derived from the intestines.…”

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Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease

et al. 2021

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Background Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn’s disease and ulcerative colitis. Methods We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulfate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn’s disease and 29 ulcerative colitis patients with active and inactive disease was included. Results In the acute and chronic dextran sulfate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn’s disease ( p < 0.05) and ulcerative colitis ( p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve: 0.81, p = 0.0009) and Crohn’s disease (area under the curve: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (Area under the curve: 0.75, p = 0.0219) and Crohn’s disease patients with active disease from those in remission (area under the curve: 0.68, p = 0.05). Conclusion PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn’s disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease

et al. 2021

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“…Relying on the basement membrane of its gills, tilapia sustains sodium homeostasis and adapts to seawater by active Na + /K + -ATPase [68]. In rat colon, sodium invasion switches on remodeling of the basement membrane [69]. The cell-adhesion molecule cadherin-11 is encoded by CDH11 [70][71][72].…”

Section: Discussionmentioning

confidence: 99%

Evidence from ileum and liver transcriptomes of resistance to high-salt and water-deprivation conditions in camel

et al. 2020

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Camels have evolved various resistance characteristics adaptive to their desert habitats. In the present study, we used high-throughput sequencing to investigate stress-induced alternative splicing events as well as different genes involved in resistance to water deprivation and salt absorption in the ileum and liver in Camelus bactrianus. Through association analyses of mRNA, miRNA and lncRNA, we sought to explicate how camels respond to high salt and water scarcity conditions. There were two modes by which genes driven by alternative splicing were enriched to molecular functions, invoking of which was potentially fixed by organ and stress types. With qRT-PCR detection, the differentially expressed MUC6, AQP5, LOC105076960, PKP4, CDH11, TENM1, SDS, LOC105061856, PLIN2 and UPP2 were screened as functionally important genes, along with miR-29b, miR-484, miR-362-5p, miR-96, miR-195, miR-128 and miR-148a. These genes contributed to cellular stress resistance, for instance by reducing water loss, inhibiting excessive import of sodium, improving protective barriers and sodium ion homeostasis, and maintaining uridine content. The underlying competing endogenous RNAs referred to LNC001664, let-7e and LOC105076960 mRNA in ileum, and LNC001438, LNC003417, LNC001770, miR-199c and TENM1 mRNA in liver. Besides competent interpretation to resistance, there may be inspirations for curing human diseases triggered by high-salt intake.

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“…54 The ECM contains numerous macromolecules (e.g., collagen, elastin, proteoglycan, and non-collagenous proteins) that control critical cellular events, such as adhesion, differentiation, migration, proliferation, and survival. 55 In the inflamed tissues, the ECM is affected by the infiltrating immune cells and the activated tissue-resident cells; this results in a remodeled ECM microenvironment with high concentrations of proinflammatory cytokines (e.g., interferons [IFNs], TNF-α, and transforming growth factor-β [TGF-β]), esterases, matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and reactive oxygen species/ reactive nitrogen species (ROS/RNS). 56 These released inflammatory regulators can modulate a wide range of ECM macromolecules.…”

Section: Immune Cells the Lamina Propria And The Extracellular Matrixmentioning

confidence: 99%

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

Yang¹,

Merlin²

2019

IJN

115

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Inflammatory bowel disease (IBD), which mainly consists of Crohn's disease and ulcerative colitis, is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The traditional treatment strategies relied on frequent administration of high dosages of medications, including antibiotics, non-steroidal anti-inflammatory drugs, biologics, and immunomodulators, with the goal of reducing inflammation. Some of these medications were effective in alleviating the early-stage inflammatory symptoms, but their long-term efficacies were compromised by the accumulation of toxicities. Recently, nanoparticle (NP)based drugs have been widely studied for their potential to solve such problems. Various mechanisms/strategies, including size-, charge-, pH-, pressure-, degradation-, ligand-receptor-, and microbiome-dependent drug delivery systems, have been exploited in preclinical studies. A certain number of NP delivery systems have sought to target drugs to the inflamed intestine. Although several NP-based drugs have entered clinical trials for the treatment of IBD, most have failed due to premature drug release, weak targeting ability, and the high immune toxicity of some of the synthetic nanomaterials that have been used to fabricate the NPs. Therefore, there is still a need for rationally designed and stable NP drug delivery system that can specifically target drugs to the disease site, prolong the drug's residence time, and minimize systemic side effects. This review will analyze the current state of the art in NP-mediated drug delivery for IBD treatment. We will focus on topics such as deliverable targets (at the tissue or cellular level) for treating inflammation; the target-homing NP materials that can interact with such targets; and the major administration routes for treating IBD. These discussions will integrate notable trends in the research and development of IBD medications, including multi-responsive NP-mediated delivery and naturally-derived targeting NPs. Finally, current challenges and future directions will be presented in the hopes of advancing the study of NP-mediated strategies for treating IBD.

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Extracellular Matrix Fragments of the Basement Membrane and the Interstitial Matrix Are Serological Markers of Intestinal Tissue Remodeling and Disease Activity in Dextran Sulfate Sodium Colitis

Cited by 28 publications

References 33 publications

Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease

Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease

Evidence from ileum and liver transcriptomes of resistance to high-salt and water-deprivation conditions in camel

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

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