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Discoidin Domain Receptors in Cardiac Development

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Discoidin Domain Receptors in Health and Disease

Abstract

Heart development is a complex process, involving temporally and spatially restricted morphogenic events that ultimately give rise to a multichambered heart. Discoidin domain receptors (DDRs) 1 and 2 are receptor tyrosine kinases which bind and are activated by multiple types of collagen, a structural protein found within the myocardium and valves of the heart. Both DDR1 and DDR2 are expressed in the developing heart, with DDR1 expression detected on both cardiac myocytes and fibroblasts, whereas DDR2 was only detected on fibroblasts. To date most studies examining DDRs during heart development have focused on the role of DDR2 in this process. DDR2 is upregulated on activated endothelial cells of cardiac cushions during epithelial-mesenchymal transformation associated with valve development. Inhibition of DDR2 results in incomplete transformation and a lack of mesenchymal cell formation in vitro; however, in vivo there appears to be a compensatory mechanism which allows for mesenchymal cell formation. DDR1 and DDR2 have both been implicated in fibroblast-mediated collagen remodeling. Additional studies are necessary to characterize the consequences of DDR1 or DDR2 deletion on cardiac function and to examine how these receptors may participate in matrix remodeling in cardiovascular disease.

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Acknowledgments

The authors would like to thank Ms. Mary Morales for technical assistance, Regeneron Pharmaceuticals for providing the DDR2 knockout mice, and the National Institutes of Health (HL73937) and the Mid-Atlantic Affiliate of the American Heart Association (0060217U and 13GRNT17070086) for funding.

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Authors and Affiliations

  1. Department of Cell Biology and Anatomy, University of South Carolina, 6439 Garners Ferry Rd., Columbia, SC, 29209, USA

    David E. Justus, Adam Hoffman, Ekaterina Mironova, Alexander Hartman, Jack G. Goldsmith, Jay D. Potts & Edie C. Goldsmith

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  1. David E. Justus
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  2. Adam Hoffman
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  3. Ekaterina Mironova
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  5. Jack G. Goldsmith
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  7. Edie C. Goldsmith
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Correspondence to Edie C. Goldsmith .

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Editors and Affiliations

  1. Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA

    Rafael Fridman

  2. Division of Cancer Biology, The Institute of Cancer Research, London, United Kingdom

    Paul H. Huang

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Justus, D.E. et al. (2016). Discoidin Domain Receptors in Cardiac Development. In: Fridman, R., Huang, P. (eds) Discoidin Domain Receptors in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-6383-6_18

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