| Title: |
Neuregulin (NRG-1β) Is Pro-Myogenic and Anti-Cachectic in Respiratory Muscles of Post-Myocardial Infarcted Swine |
| Authors: |
Cristi L. Galindo, Van Thuan Nguyen, Braxton Hill, Ethan Easterday, John H. Cleator, Douglas B. Sawyer |
| Source: |
Biology, Vol 11, Iss 5, p 682 (2022) |
| Publisher Information: |
MDPI AG, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
myocardial infarction, neuregulin, glial growth factor 2, pre-clinical therapy, skeletal muscle, gene expression, Biology (General), QH301-705.5 |
| More Details: |
Neuregulin-1β (NRG-1β) is a growth and differentiation factor with pleiotropic systemic effects. Because NRG-1β has therapeutic potential for heart failure and has known growth effects in skeletal muscle, we hypothesized that it might affect heart failure-associated cachexia, a severe co-morbidity characterized by a loss of muscle mass. We therefore assessed NRG-1β’s effect on intercostal skeletal muscle gene expression in a swine model of heart failure using recombinant glial growth factor 2 (USAN-cimaglermin alfa), a version of NRG-1β that has been tested in humans with systolic heart failure. Animals received one of two intravenous doses (0.67 or 2 mg/kg) of NRG-1β bi-weekly for 4 weeks, beginning one week after infarct. Based on paired-end RNA sequencing, NRG-1β treatment altered the intercostal muscle gene expression of 581 transcripts, including genes required for myofiber growth, maintenance and survival, such as MYH3, MYHC, MYL6B, KY and HES1. Importantly, NRG-1β altered the directionality of at least 85 genes associated with cachexia, including myostatin, which negatively regulates myoblast differentiation by down-regulating MyoD expression. Consistent with this, MyoD was increased in NRG-1β-treated animals. In vitro experiments with myoblast cell lines confirmed that NRG-1β induces ERBB-dependent differentiation. These findings suggest a NRG-1β-mediated anti-atrophic, anti-cachexia effect that may provide additional benefits to this potential therapy in heart failure. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2079-7737 |
| Relation: |
https://www.mdpi.com/2079-7737/11/5/682; https://doaj.org/toc/2079-7737 |
| DOI: |
10.3390/biology11050682 |
| Access URL: |
https://doaj.org/article/4b93cf3be5624b8a9c83d11b95ef69c1 |
| Accession Number: |
edsdoj.4b93cf3be5624b8a9c83d11b95ef69c1 |
| Database: |
Directory of Open Access Journals |
