Matricellular Protein SPARCL1 Regulates Blood Vessel Integrity and Antagonizes Inflammatory Bowel Disease. Issue 9 (4th January 2021)

• Record Type: Journal Article
• Authors: Regensburger, Daniela; Tenkerian, Clara; Pürzer, Victoria; Schmid, Benjamin; Wohlfahrt, Thomas; Stolzer, Iris; López-Posadas, Rocío; Günther, Claudia; Waldner, Maximilian J; Becker, Christoph; Sticht, Heinrich; Petter, Katja; Flierl, Christian; Gass, Tobias; Thoenissen, Tim; Geppert, Carol I; Britzen-Laurent, Nathalie; Méniel, Valérie S; Ramming, Andreas; Stürzl, Michael; Naschberger, Elisabeth
• Is Part Of: Inflammatory bowel diseases. Volume 27:Issue 9(2021)
• Page Start: 1491
• Page End: 1502
• Publication Date: 2021-01-04
• Subjects: angiogenesis -- blood vessel -- DSS colitis -- endothelial cell -- inflammatory bowel disease -- permeability -- SPARCL1; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1093/ibd/izaa346
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract: 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.