Expression and activation of MMP -2, -3, -9, -14 are induced in rat colon after abdominal X-irradiation
| Autor: | Denis Mathé, Marc Benderitter, Marie-Catherine Vozenin-Brotons, Marie Vandamme, Carine Strup-Perrot |
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| Přispěvatelé: | Laboratoire de Radiopathologie et Thérapies Expérimentales, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut Gustave Roussy (IGR) |
| Rok vydání: | 2006 |
| Předmět: |
Male
Pathology interleukin 1beta Plasmin [SDV]Life Sciences [q-bio] medicine.medical_treatment Wistar Matrix metalloproteinase Extracellular matrix 0302 clinical medicine tissue inhibitor of metalloproteinase 1 tissue inhibitor of metalloproteinase 2 rat Intestinal Mucosa enzyme inhibition chemistry.chemical_classification 0303 health sciences tumor necrosis factor alpha messenger RNA Reverse Transcriptase Polymerase Chain Reaction article Gastroenterology zymography enzyme activity X ray Extracellular Matrix Cytokine colon mucosa priority journal Matrix Metalloproteinase 9 real time polymerase chain reaction 030220 oncology & carcinogenesis immunohistochemistry plasminogen Matrix Metalloproteinase 2 Immunohistochemistry Matrix Metalloproteinase 3 matrix metalloproteinase 14 ionizing radiation radiation dose medicine.drug medicine.medical_specialty Colon animal experiment Gelatinase A Matrix Metalloproteinase Inhibitors Biology animal tissue enzyme degradation gelatinase B reverse transcription polymerase chain reaction 03 medical and health sciences Plasminogen Activator Inhibitor 1 medicine Animals extracellular fluid Zymography Rats Wistar protein expression gelatinase A plasmin 030304 developmental biology nonhuman Tissue Inhibitor of Metalloproteinase-1 Tumor Necrosis Factor-alpha stromelysin basement membrane Molecular biology Matrix Metalloproteinases Rats Enzyme Activation Enzyme chemistry X irradiation abdomen Interleukin-1 |
| Zdroj: | Scandinavian journal of gastroenterology Scandinavian journal of gastroenterology, 2006, 41 (1), pp.60-70. ⟨10.1080/00365520510023963⟩ |
| ISSN: | 1502-7708 0036-5521 |
| Popis: | Objective. Colonic response to single-dose irradiation is characterized by epithelial denudation followed by restitution. Extracellular matrix (ECM) remodeling is involved in both of these phases. The aim of this study was to characterize the contribution of matrix metalloproteinases (MMPs) and of their stimulatory and inhibitory pathways in radiation-induced ECM remodeling in colonic tissue. Material and methods. Rats were irradiated with single-dose 10 Gy X-rays to the abdomen. Activity, localization, and mRNA levels of MMPs and molecules involved in their activation and inhibition (plasmin/plasminogen; TIMPs), of inflammatory mediators (IL-1β, TNF-α) in the distal colon, 1, 3, and 7 days after irradiation were analyzed using a combination of approaches including zymography, immunohistochemistry, and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results. The main finding of this study is that radiation-induced alteration of the mucosal structure is concomitant with local increased expression and activation of MMP subtypes involved in basement membrane degradation (MMP-2, -3, and -9). We investigated MMP-2 activation pathways and found an early increase in mRNA levels of soluble inflammatory mediators (TNF-α and IL-1β). Furthermore, transcription and activity of MMP-2 activating molecules, such as MMP-14, and molecules involved in the plasminogen/plasmin system were found to increase during the denudation phase. Interestingly, induction of MMP inhibitors TIMP-1 and PAI-1 was observed during the restitution phase. MMP inhibitors may be able to stop acute wound healing response by inhibiting ECM degradation. Conclusions. This study brings new insights into ECM remodeling in the colon after exposure to ionizing radiation and highlights the role of MMP subtypes specialized in basement membrane degradation. © 2006 Taylor & Francis. |
| Databáze: | OpenAIRE |
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