NADPH oxidase and TSP1

Despite the increasing evidence supporting the role of matricellular proteins, such as thrombospondin 1 (TSP1) in vascular disease, their potential to stimulate ROS generation in vascular tissue and their pathological significance in oxidative stress−mediated vascular dysfunction remained unknown. Data from our group suggested that this protein could act as a ligand for NADPH oxidase activation through the specific engagement of integrin-associated protein CD47. This interaction represents a highly regulated process of ROS stimulation and blood flow regulation promoted through the direct TSP1/CD47-mediated activation of Nox1.

Bauer EM, Qin Y, Miller TW, Bandle RW, Csanyi G, Pagano PJ, Bauer PM, Schnermann J, Roberts DD, Isenberg JS. Thrombospondin-1 supports blood pressure by limiting eNOS activation and endothelial-dependent vasorelaxation. Cardiovasc Res. 2010; 88(3):471-81. PubMed PMID: 20610415, PMCID: PMC2972685

Csányi G, Yao M, Rodríguez AI, Al Ghouleh I, Sharifi-Sanjani M, Frazziano G, Huang X, Kelley EE, Isenberg JS, Pagano PJ. Thrombospondin-1 regulates blood flow via CD47 receptor-mediated activation of NADPH oxidase 1. Arterioscler Thromb Vasc Biol. 2012 Dec; 32(12):2966-73. PubMed PMID: 23087362, PMCID: PMC4394361

Rogers NM, Sharifi-Sanjani M, Csányi G, Pagano PJ, Isenberg JS. Thrombospondin-1and CD47 regulation of cardiac, pulmonary and vascular responses in health and disease. Matrix Biol. 2014; 37:92-101. PubMed PMID: 24418252, PMCID: PMC4096433

Yao M, Rogers NM, Csányi G, Rodriguez AI, Ross MA, St Croix C, Knupp H, Novelli EM, Thomson AW, Pagano PJ, Isenberg JS. Thrombospondin-1 activation of signal-regulatory protein-α stimulates reactive oxygen species production and promotes renal ischemia reperfusion injury. J Am Soc Nephrol. 2014; 25(6):1171-86. PubMed PMID: 24511121, PMCID: PMC4033366