Growth factors in the therapy of bronchopulmonary dyplasia
Autor: | Anne Chetty, Vineet Bhandari, Heber C. Nielsen |
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Rok vydání: | 2020 |
Předmět: |
business.industry
Growth factor medicine.medical_treatment medicine.disease Vascular endothelial growth factor CTGF chemistry.chemical_compound chemistry Bronchopulmonary dysplasia medicine Cancer research Hepatocyte growth factor Signal transduction business Elafin medicine.drug Transforming growth factor |
Zdroj: | Tantalizing Therapeutics in Bronchopulmonary Dysplasia ISBN: 9780128189870 |
DOI: | 10.1016/b978-0-12-818987-0.00008-4 |
Popis: | Several growth factors have been associated with human bronchopulmonary dysplasia (BPD), while a select few have been shown to have a causal role in the pathogenesis of experimental BPD in a variety of animal models (mice, rat, lamb, rhesus monkey and baboon). These include connective tissue growth factor (CTGF), hypoxia-inducible factor (HIF)-1α, pulmonary hepatocyte growth factor (HGF), transforming growth factor (TGF)β1, insulin-like growth factor (IGF), and vascular endothelial growth factor (VEGF). Although inhaled nitric oxide (iNO; downstream of VEGF signaling) use had disappointing clinical outcomes when used for prevention of BPD, potential new targets involving VEGF signaling could be activation of the HIF signaling pathway either by inhibition of prolyl hydroxylase domain-containing proteins (PHDs) by using FG-4095 or by using sildenafil. Clinical evidence for a mechanistic role of other growth factors and pathways does not exist, but laboratory studies suggest potential roles for many. These include the following: the anti-TGFβ antibody ID11, curcumin, elafin and etanercept are possible future therapeutics that have not yet entered the clinical arena of BPD. Recombinant human (rh) HGF could have a possible role, though currently there are no clinical trials targeting the HGF signaling pathway. Inhibition of CTGF and/or β-catenin (using ICG001) signaling appears to hold some promise based on the experimental data. The recent report that rhIGF-1/IGFB-3 reverses the lung and pulmonary resistance changes of experimental BPD in neonatal rats and the promising results of a phase II clinical trial of the same have reawakened interest in the manipulation if IGF-1 signaling to combat BPD. Currently, the most anticipated results are those of the concomitant administration of recombinant human IGF-1 (rhIGF-1) and IGF binding protein (rhIGFBP)-3 in an ongoing clinical trial for the prevention of BPD. |
Databáze: | OpenAIRE |
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