scholarly journals Imaging the Alternatively Spliced D Domain of Tenascin C in Preclinical Models of Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Liang Zhang ◽  
Calvin S. Pohl ◽  
Kristoff T. Homan ◽  
Victor Z. Sun ◽  
Stephanie M. Gaudette ◽  
...  
Keyword(s):  
Near Infrared ◽  
Cellular Level ◽  
Imaging Data ◽  
Specific Expression ◽  
Tenascin C ◽  
Molecular Imaging Agents ◽  
Promising Target ◽  
Bowel Diseases ◽  
Alternatively Spliced ◽  
Inflammatory Bowel

Abstract Purpose To image colon-expressed alternatively spliced D domain of tenascin C in preclinical colitis models using near infrared (NIR) labeled targeted molecular imaging agents.Methods Human IgG and scFv fusion proteins specific to the alternatively spliced D domain of tenascin C were generated. Immunohistochemistry identified disease-specific expression of this extracellular matrix in mouse colitis models. Proteins were labeled with the NIR fluorophore IRDye 800CW via amine chemistry and intravenously dosed to evaluate targeting specificity in preclinical rodent and primate colitis models.Results The NIR labeled proteins successfully targeted colonic lesions in a murine model of colitis and appeared as distinct punctate spots. Co-administration of a blocking dose reduced the whole colon standardized uptake of the fluorescent dose >7-fold in mouse models. Estimates suggest local expression at >100 nM in diseased mouse colon. Macroscopic targeting specificity was not observed in diseased primate colon. Cellular level specificity was assessed via microscopy and immunohistochemistry.Conclusion Our imaging data suggest the alternatively spliced D domain of tenascin C is a promising target for delivery-based applications in inflammatory bowel diseases.

Interleukin-34 sustains inflammatory pathways in the gut

2015 ◽  
Vol 129 (3) ◽  
pp. 271-280 ◽  
Author(s):  
Eleonora Franzè ◽  
Ivan Monteleone ◽  
Maria Laura Cupi ◽  
Pamela Mancia ◽  
Flavio Caprioli ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Therapeutic Interventions ◽  
Inflammatory Pathways ◽  
Promising Target ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Interleukin-34, is highly synthesized in inflamed gut of patients with inflammatory bowel diseases, contributes to amplify the mucosal pathogenic response, and therefore could be a promising target for therapeutic interventions in patients with these disorders.

scholarly journals Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via β1-Integrin Activation in Fibroblasts

2019 ◽  
Vol 20 (11) ◽  
pp. 2752 ◽  
Author(s):  
Motomichi Fujita ◽  
Yuka Ito-Fujita ◽  
Takuya Iyoda ◽  
Manabu Sasada ◽  
Yuko Okada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Diseases ◽  
Matricellular Protein ◽  
Β1 Integrin ◽  
Integrin Activation ◽  
Stromal Fibroblasts ◽  
Tenascin C ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases increase the risk of colorectal cancer and colitis-associated colorectal cancer (CAC). Tenascin-C, a matricellular protein, is highly expressed in inflammatory bowel diseases, especially colorectal cancer. However, the role of tenascin-C in the development of CAC is not yet fully understood. We previously showed that a peptide derived from tenascin-C, peptide TNIIIA2, induces potent and sustained activation of β1-integrin. Moreover, we recently reported that peptide TNIIIA2 promotes invasion and metastasis in colon cancer cells. Here, we show the pathological relevance of TNIIIA2-related functional site for the development of CAC. First, expression of the TNIIIA2-containing TNC peptides/fragments was detected in dysplastic lesions of an azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model. In vitro experiments demonstrated that conditioned medium from peptide TNIIIA2-stimulated human WI-38 fibroblasts induced malignant transformation in preneoplastic epithelial HaCaT cells. Indeed, these pro-proliferative effects stimulated by peptide TNIIIA2 were abrogated by peptide FNIII14, which has the ability to inactivate β1-integrin. Importantly, peptide FNIII14 was capable of suppressing polyp formation in the AOM/DSS model. Therefore, tenascin-C-derived peptide TNIIIA2 may contribute to the formation of CAC via activation of stromal fibroblasts based on β1-integrin activation. Peptide FNIII14 could represent a potential prophylactic treatment for CAC.

Compartment-specific Expression of ALCAM (CD166) in Inflammatory Bowel Diseases

2010 ◽  
Vol 135 ◽  
pp. S100
Author(s):  
Felix Lasitschka ◽  
Kristina Schroeder ◽  
Thomas Giese ◽  
Sonja Schwarz ◽  
Jutta Schroeder-Braunstein ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Specific Expression ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Localization and Activity of Inflammatory Bowel Disease Using 111ln Leukocyte Imaging

1988 ◽  
Vol 27 (03) ◽  
pp. 83-86 ◽  
Author(s):  
B. Briele ◽  
F. Wolf ◽  
H. J. Biersack ◽  
F. F. Knapp ◽  
A. Hotze
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Cell Uptake ◽  
Disease Extent ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Leukocyte Imaging

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.

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