Revisiting the Role for HIF Stabilizers in Bronchopulmonary Dysplasia

Abstract

of patients with CF. The fact that the inhibition or the genetic ablation of genes controlling sphingolipid synthesis have been associated with hepatic steatosis suggests that the long-term effects of sphingolipid metabolic deficiencies may become associated with excessive hepatic triglyceride accumulation (16).How are CFTR mutations linked to deficient sphingomyelin hydrolysis, accumulated ceramide, deficient acid ceramidase, and decreased sphingosine? Answers to this question may provide important information about the essential role of sphingomyelin metabolism in cell membrane function in CF. Furthermore, the impact of lipid accumulation may pose an important insight into CFTR pathophysiology beyond that which is addressed by current modulator therapy, contributing to therapeutic outcomes. Gardner uses innovative technology to explore the role of sphingomyelin, ceramide accumulation, and deficient sphingosine production in cellular function and pathophysiology in CF. The use of recombinant acid ceramidase as a potential antiinflammatory therapeutic makes sense from a basic biological standpoint, associating the intricacies of cellular design and the impact of deficient CFTR on cell function. The answer lies in the details of understanding CFTR mechanistically beyond ion transport in the hunt for management of all of the disease-associated pathologies for individuals who suffer from CF. n

Involvement of HIF1 stabilization and VEGF signaling modulated by Grx‐1 in murine model of bronchopulmonary dysplasia

“…Pharmacological HIF stabilization, which increased the expression of HIF‐1α, exhibited therapeutic benefit in experimental BPD through angiogenic growth and alveolar development in the experimental model of BPD (Choi et al, 2015; Grover et al, 2007; Mathew, 2020). HIF‐1α deletion was associated with respiratory distress and depression of surfactant synthesis in the neonatal lung (Boucherat et al, 2020), suggesting a critical role for HIFs in the surfactant production and lung maturation. However, the modulation role of Grx1 on HIF‐1α stability involved in the abnormal vascular development in BPD pathogenesis has not been explored.…”

Role of vitamin D–vitamin D receptor signaling on hyperoxia‐induced bronchopulmonary dysplasia in neonatal rats

“…HIF‐1α participates in lung growth and development in BPD. It also induces angiogenesis by the regulation of VEGF 36,37 . The mRNA and protein levels of HIF‐1α in lung tissues were then determined.…”