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Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine

by 1, 1,2,3,4,* and 1,3,*
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia
Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2145, Australia
Renal and Transplant Unit, Westmead Hospital, Westmead, NSW 2145, Australia
Starzl Transplant Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA
Authors to whom correspondence should be addressed.
Academic Editor: Hironobu Yamashita
Int. J. Mol. Sci. 2021, 22(8), 4062;
Received: 11 February 2021 / Revised: 19 March 2021 / Accepted: 30 March 2021 / Published: 14 April 2021
(This article belongs to the Special Issue Proteolysis of Extracellular Matrix in Human Disease)
Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed. View Full-Text
Keywords: thrombospondin-1 (TSP1; THBS1); CD47 (IAP); matricellular; fibrosis; kidney injury; glucose homeostasis; ageing; reactive oxygen species thrombospondin-1 (TSP1; THBS1); CD47 (IAP); matricellular; fibrosis; kidney injury; glucose homeostasis; ageing; reactive oxygen species
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MDPI and ACS Style

Kale, A.; Rogers, N.M.; Ghimire, K. Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine. Int. J. Mol. Sci. 2021, 22, 4062.

AMA Style

Kale A, Rogers NM, Ghimire K. Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine. International Journal of Molecular Sciences. 2021; 22(8):4062.

Chicago/Turabian Style

Kale, Atharva, Natasha M. Rogers, and Kedar Ghimire. 2021. "Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine" International Journal of Molecular Sciences 22, no. 8: 4062.

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