LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Autophagy inducer activates Nrf2-ARE pathway to attenuate aberrant alveolarization in neonatal rats with bronchopulmonary dysplasia.

Photo by tcwillmott from unsplash

Abstract Aims Bronchopulmonary dysplasia (BPD) is a severe respiratory complication in preterm infants. This study reveals the molecular mechanism of autophagic agonists regulating the Nrf2-ARE pathway via p62 to improve… Click to show full abstract

Abstract Aims Bronchopulmonary dysplasia (BPD) is a severe respiratory complication in preterm infants. This study reveals the molecular mechanism of autophagic agonists regulating the Nrf2-ARE pathway via p62 to improve alveolar development in BPD rats. Main methods Newborn Sprague-Dawley rats were randomly exposed to a hyperoxic environment (FiO2 = 0.85) for 14 days and rapamycin (RAPA) was intraperitoneally injected on alternate days into hyperoxia-exposed mice. Alveolar development was assessed using HE and RAC values. Markers associated with the p62-Keap1-Nrf2-ARE pathway were detected by western blot, immunohistochemistry, and RT-PCR. Co-localization of proteins was determined using double immunofluorescence staining. Key findings At the levels of lung tissue and primary type II alveolar epithelial cells, the enhanced binding between phosphorylated p62 and Keap1 disrupted the nuclear transport of Nrf2. The activated Nrf2 was insufficient to reverse alveolar simplification. The autophagy agonist was able to inhibit p62 phosphorylation, promote Keap1 degradation, increase Nrf2 nuclear transport, augment downstream antioxidant enzyme expression, and enhance antioxidant capacity, thereby improving the simplification of alveolar structure in BPD rats. Significance The use of autophagy agonists to enhance the Nrf2-ARE pathway activity and promote alveolar development could be a novel target in antioxidant therapy for BPD.

Keywords: autophagy inducer; nrf2 pathway; bpd; bronchopulmonary dysplasia; alveolar development

Journal Title: Life Sciences
Year Published: 2020

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.