Additional Funding Sources
The project described was supported by the Center of Excellence in Biomedical Research through the Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant Nos. P20GM109095 and P20GM103408 and the National Science Foundation S-STEM Gateway Scholarships in Biological Sciences under Grant Award No. DUE-1644233. Further support was received from the Center of Excellence in Biomedical Research through the Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant Nos. P20GM109095 and P20GM103408 and the National Science Foundation S-STEM Gateway Scholarships in Biological Sciences under Grant Award No. DUE-1644233. We also acknowledge support from the Biomolecular Research Center at Boise State University, Matrix Biology - Center of Biomedical Research Excellence, the Idaho State Board of Education, and Idaho College of Osteopathic Medicine.
Abstract
Cellular Communication Network Factor 2 (CCN2) is a matricellular protein encompassing many cellular functions, including extracellular matrix (ECM) deposition. The role of CCN2 has been investigated in numerous studies, but one region of CCN2 that has not been fully investigated is the role of CCN2 when exposed to cardiotoxic chemotherapeutics and how it affects the cardiac ECM. During chronic cardiac inflammation, CCN2 is activated, which eventually leads to cardiac fibrosis and remodeling. Consequently, this result has been shown to markedly reduce the efficacy of cardiac function, contributing to cardiomyopathy when severe. Doxorubicin (DOX) is an anthracycline chemotherapeutic commonly used to treat many cancers, such as breast and blood cancers. Fibroblasts are one of the leading cell lines to partake in ECM regulation, especially in the heart. In this study, we investigated the effects of DOX on CCN2 expression in NIH3T3 mouse embryonic fibroblast and primary mouse cardiac fibroblast. We administered DOX treatments and performed protein and RNA isolation on our cell lines for the use of western blot and RT-qPCR, respectively. A focus was placed on CCN2 as well as other proteins established to promote CCN2 protein and gene expression. Lastly, we also investigated ECM proteins commonly expressed in the presence of CCN2. As a result, our study explores DOX’s adverse effects on the cardiac extracellular matrix by means of disruption of ECM depositor CCN2.
Investigating the Cardiotoxic Behavior of Doxorubicin on the ECM Through CCN2 Expression in Cardiac Fibroblasts
Cellular Communication Network Factor 2 (CCN2) is a matricellular protein encompassing many cellular functions, including extracellular matrix (ECM) deposition. The role of CCN2 has been investigated in numerous studies, but one region of CCN2 that has not been fully investigated is the role of CCN2 when exposed to cardiotoxic chemotherapeutics and how it affects the cardiac ECM. During chronic cardiac inflammation, CCN2 is activated, which eventually leads to cardiac fibrosis and remodeling. Consequently, this result has been shown to markedly reduce the efficacy of cardiac function, contributing to cardiomyopathy when severe. Doxorubicin (DOX) is an anthracycline chemotherapeutic commonly used to treat many cancers, such as breast and blood cancers. Fibroblasts are one of the leading cell lines to partake in ECM regulation, especially in the heart. In this study, we investigated the effects of DOX on CCN2 expression in NIH3T3 mouse embryonic fibroblast and primary mouse cardiac fibroblast. We administered DOX treatments and performed protein and RNA isolation on our cell lines for the use of western blot and RT-qPCR, respectively. A focus was placed on CCN2 as well as other proteins established to promote CCN2 protein and gene expression. Lastly, we also investigated ECM proteins commonly expressed in the presence of CCN2. As a result, our study explores DOX’s adverse effects on the cardiac extracellular matrix by means of disruption of ECM depositor CCN2.