Matricellular Protein SPARCL1 Regulates Blood Vessel Integrity and Antagonizes Inflammatory Bowel Disease
| Autor: | Carol Geppert, Rocío López-Posadas, Andreas Ramming, Clara Tenkerian, Heinrich Sticht, Elisabeth Naschberger, Victoria Pürzer, Claudia Günther, Katja Petter, Tim Thoenissen, Christoph Becker, Benjamin Schmid, Thomas Wohlfahrt, Tobias Gass, Valerie Meniel, Christian Flierl, Maximilian J. Waldner, Nathalie Britzen-Laurent, Iris Stolzer, Michael Stürzl, Daniela Regensburger |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
DSS colitis Angiogenesis SPARCL1 Inflammation Inflammatory bowel disease 03 medical and health sciences angiogenesis Mice 0302 clinical medicine blood vessel inflammatory bowel disease Immunology and Allergy Medicine Animals Colitis Ibdjnl/4 AcademicSubjects/MED00260 Sprouting angiogenesis Mice Knockout Extracellular Matrix Proteins Neovascularization Pathologic business.industry Matricellular protein Calcium-Binding Proteins Dextran Sulfate Gastroenterology medicine.disease Cell biology Endothelial stem cell 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis cardiovascular system endothelial cell medicine.symptom permeability business Basic Science Research Blood vessel |
| Zdroj: | Inflammatory Bowel Diseases |
| ISSN: | 1536-4844 1078-0998 |
| Popis: | Background The understanding of vascular plasticity is key to defining the role of blood vessels in physiologic and pathogenic processes. In the present study, the impact of the vascular quiescence marker SPARCL1 on angiogenesis, capillary morphogenesis, and vessel integrity was evaluated. Methods Angiogenesis was studied using the metatarsal test, an ex vivo model of sprouting angiogenesis. In addition, acute and chronic dextran sodium sulfate colitis models with SPARCL1 knockout mice were applied. Results This approach indicated that SPARCL1 inhibits angiogenesis and supports vessel morphogenesis and integrity. Evidence was provided that SPARCL1-mediated stabilization of vessel integrity counteracts vessel permeability and inflammation in acute and chronic dextran sodium sulfate colitis models. Structure-function analyses of purified SPARCL1 identified the acidic domain of the protein necessary for its anti-angiogenic activity. Conclusions Our findings inaugurate SPARCL1 as a blood vessel–derived anti-angiogenic molecule required for vessel morphogenesis and integrity. SPARCL1 opens new perspectives as a vascular marker of susceptibility to colitis and as a therapeutic molecule to support blood vessel stability in this disease. |
| Databáze: | OpenAIRE |
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