Amphiregulin Exerts Proangiogenic Effects in Developing Murine Lungs
Interrupted lung angiogenesis is a hallmark of bronchopulmonary dysplasia (BPD); however, druggable targets that can rescue this phenotype remain elusive. Thus, our investigation focused on amphiregulin (Areg), a growth factor that mediates cellular proliferation, differentiation, migration, surviva...
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MDPI AG,
2024-01-01T00:00:00Z.
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| LEADER | 00000 am a22000003u 4500 | ||
|---|---|---|---|
| 001 | doaj_a43368c33842488aba3f7e69fd81e64c | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Shyam Thapa |e author |
| 700 | 1 | 0 | |a Nithyapriya Shankar |e author |
| 700 | 1 | 0 | |a Amrit Kumar Shrestha |e author |
| 700 | 1 | 0 | |a Monish Civunigunta |e author |
| 700 | 1 | 0 | |a Amos S. Gaikwad |e author |
| 700 | 1 | 0 | |a Binoy Shivanna |e author |
| 245 | 0 | 0 | |a Amphiregulin Exerts Proangiogenic Effects in Developing Murine Lungs |
| 260 | |b MDPI AG, |c 2024-01-01T00:00:00Z. | ||
| 500 | |a 10.3390/antiox13010078 | ||
| 500 | |a 2076-3921 | ||
| 520 | |a Interrupted lung angiogenesis is a hallmark of bronchopulmonary dysplasia (BPD); however, druggable targets that can rescue this phenotype remain elusive. Thus, our investigation focused on amphiregulin (Areg), a growth factor that mediates cellular proliferation, differentiation, migration, survival, and repair. While Areg promotes lung branching morphogenesis, its effect on endothelial cell (EC) homeostasis in developing lungs is understudied. Therefore, we hypothesized that Areg promotes the proangiogenic ability of the ECs in developing murine lungs exposed to hyperoxia. Lung tissues were harvested from neonatal mice exposed to normoxia or hyperoxia to determine Areg expression. Next, we performed genetic loss-of-function and pharmacological gain-of-function studies in normoxia- and hyperoxia-exposed fetal murine lung ECs. Hyperoxia increased <i>Areg</i> mRNA levels and Areg+ cells in whole lungs. While <i>Areg</i> expression was increased in lung ECs exposed to hyperoxia, the expression of its signaling receptor, <i>epidermal growth factor receptor</i>, was decreased, indicating that hyperoxia reduces <i>Areg</i> signaling in lung ECs. <i>Areg deficiency</i> potentiated hyperoxia-mediated anti-angiogenic effects. In contrast, Areg treatment increased extracellular signal-regulated kinase activation and exerted proangiogenic effects. In conclusion, Areg promotes EC tubule formation in developing murine lungs exposed to hyperoxia. | ||
| 546 | |a EN | ||
| 690 | |a angiogenesis | ||
| 690 | |a amphiregulin | ||
| 690 | |a fetal murine lung endothelial cells | ||
| 690 | |a hyperoxia | ||
| 690 | |a bronchopulmonary dysplasia | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Antioxidants, Vol 13, Iss 1, p 78 (2024) | |
| 787 | 0 | |n https://www.mdpi.com/2076-3921/13/1/78 | |
| 787 | 0 | |n https://doaj.org/toc/2076-3921 | |
| 856 | 4 | 1 | |u https://doaj.org/article/a43368c33842488aba3f7e69fd81e64c |z Connect to this object online. |