Premium
Epidermal Growth Factor Receptor Family Signaling in the Regenerating Axolotl Lung
Author(s) -
Jensen Tyler Barry,
Giunta Peter,
Schultz Natalie Grace,
Wong Hilary,
Monaghan James
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.615.8
Subject(s) - axolotl , epidermal growth factor receptor , neuregulin , regeneration (biology) , epidermal growth factor , biology , lung , erbb4 , microbiology and biotechnology , downregulation and upregulation , cancer research , immunology , pathology , receptor , signal transduction , medicine , receptor tyrosine kinase , genetics , gene
Efforts to elucidate novel mechanisms of lung regeneration have the potential to change lives and transform health care. The axolotl salamander, Ambystoma mexicanum , has long been held as a model organism of vertebrate regeneration, particularly in limbs. It is thought that they regenerate all of their tissues, but exploration of lung regeneration has not been previously characterized. In this study, we have conducted experiments demonstrating that axolotls are capable of significant lung regeneration after amputation of the distal third of the lung. We have shown the importance of ErbB signaling in the lung tissue, and the potential of neuregulin signaling in the induction of new lung cells. Proliferation was observed to be a global response throughout the lung tissue of the axolotl after lung injury. This would suggest the regeneration utilizes a compensatory mechanism. ErbB4 mRNA was found to be upregulated at one week post‐amputation in the axolotl lung above other EGF family receptors. Injected neuregulin‐1 was mitogenic to lung tissue and upregulated ErbB4 as seen in lung injury. When we inhibited ErbB2, we found that lung regeneration was halted. Epidermal growth factor signaling is crucial for regeneration to take place, specifically through the ErbB2:ErbB4 epidermal growth factor family receptor heterodimer. Neuregulin‐1 can induce proliferation in the lung, and is a likely candidate to exert molecular control over lung regeneration. Support or Funding Information NSF Grant #1558017 to JRM