The Wellesley News (06-10-1957)

https://repository.wellesley.edu/wcnews/1157/thumbnail.jp

The role of ErbB4 in cancer

The epidermal growth factor receptor family consists of four members, ErbB1 (epidermal growth factor receptor-1), ErbB2, ErbB3, and ErbB4, which all have been found to play important roles in tumor development. ErbB4 appears to be unique among these receptors, because it is the only member with growth inhibiting properties. ErbB4 plays well-defined roles in normal tissue development, in particular the heart, the nervous system, and the mammary gland system. In recent years, information on the role of ErbB4 in a number of tumors has emerged and its general direction points towards a tumor suppressor role for ErbB4. However, there are some controversies and conflicting data, warranting a review on this topic.info:eu-repo/semantics/publishe

The role of ErbB4 in cancer.

The epidermal growth factor receptor family consists of four members, ErbB1 (epidermal growth factor receptor-1), ErbB2, ErbB3, and ErbB4, which all have been found to play important roles in tumor development. ErbB4 appears to be unique among these receptors, because it is the only member with growth inhibiting properties. ErbB4 plays well-defined roles in normal tissue development, in particular the heart, the nervous system, and the mammary gland system. In recent years, information on the role of ErbB4 in a number of tumors has emerged and its general direction points towards a tumor suppressor role for ErbB4. However, there are some controversies and conflicting data, warranting a review on this topic.info:eu-repo/semantics/publishe

The role of endothelial autocrine NRG1/ERBB4 signaling in cardiac remodeling

Neuregulin-1 (NRG1) is a paracrine growth factor, secreted by cardiac endothelial cells (ECs) in conditions of cardiac overload/injury. The current concept is that the cardiac effects of NRG1 are mediated by activation of ERBB4/ERBB2 receptors on cardiomyocytes. However, recent studies have shown that paracrine effects of NRG1 on fibroblasts and macrophages are equally important. Here, we hypothesize that NRG1 autocrine signaling plays a role in cardiac remodeling. We generated EC–specific Erbb4 knockout mice to eliminate endothelial autocrine ERBB4 signaling without affecting paracrine NRG1/ERBB4 signaling in the heart. We first observed no basal cardiac phenotype in these mice up to 32 weeks. We next studied these mice following transverse aortic constriction (TAC), exposure to angiotensin II (Ang II) or myocardial infarction in terms of cardiac performance, myocardial hypertrophy, myocardial fibrosis and capillary density. In general, no major differences between EC–specific Erbb4 knockout mice and control littermates were observed. However, 8 weeks following TAC both myocardial hypertrophy and fibrosis were attenuated by EC–specific Erbb4 deletion, albeit these responses were normalized after 20 weeks. Similarly, 4 weeks after Ang II treatment myocardial fibrosis was less pronounced compared to control littermates. These observations were supported by RNA-sequencing experiments on cultured endothelial cells showing that NRG1 controls the expression of various hypertrophic and fibrotic pathways. Overall, this study shows a role of endothelial autocrine NRG1/ERBB4 signaling in the modulation of hypertrophic and fibrotic responses during early cardiac remodeling. This study contributes to understanding the spatio-temporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury

Mechanisms of the Multitasking Endothelial Protein NRG-1 as a Compensatory Factor During Chronic Heart Failure.

Heart failure is a complex syndrome whose phenotypic presentation and disease progression depends on a complex network of adaptive and maladaptive responses. One of these responses is the endothelial release of NRG (neuregulin)-1-a paracrine growth factor activating ErbB2 (erythroblastic leukemia viral oncogene homolog B2), ErbB3, and ErbB4 receptor tyrosine kinases on various targets cells. NRG-1 features a multitasking profile tuning regenerative, inflammatory, fibrotic, and metabolic processes. Here, we review the activities of NRG-1 on different cell types and organs and their implication for heart failure progression and its comorbidities. Although, in general, effects of NRG-1 in heart failure are compensatory and beneficial, translation into therapies remains unaccomplished both because of the complexity of the underlying pathways and because of the challenges in the development of therapeutics (proteins, peptides, small molecules, and RNA-based therapies) for tyrosine kinase receptors. Here, we give an overview of the complexity to be faced and how it may be tackled.info:eu-repo/semantics/publishe