Bronchopulmonary dysplasia of the premature baby

Endothelin-1 Signaling Promotes Fibrosis In Vitro in a Bronchopulmonary Dysplasia Model by Activating the Extrinsic Coagulation Cascade

“…The higher levels of TF and CTGF in supernatants collected on the third day of the disease provide evidence for a correlation between these two molecules. Such a finding may be related to the previously reported accumulation of PMNs in the alveolar space and myofibroblasts in the fibrotic lesions of BPD (35). Despite the variability of TF expression in BPD BALF cells at day 3 (which could be attributed to the differential expression of inflammatory mediators in the alveolar microenvironment), we found a parallel reduction of TF levels and neutrophil numbers in BALF during the course of the disease.…”

“…The critical role of myofibroblasts in the fibrotic process (42) and their previously documented presence in BPD lesions in infants (35) prompted us to select this cell type for our in vitro studies. Given that these cells share common functions, even when derived from different tissues (18), we chose to perform the majority of our in vitro studies in primary cultures of myofibroblasts from human colon because of their availability, and to reproduce the key findings in primary lung myofibroblasts because of the rarity of sample.…”

“…Myofibroblasts are found in fibrotic lesions from BPD infants on the fourth day of the disease course (35). Given that these cells are highly involved in fibrosis, we asked how the possible interplay between the TF pathway and the fibrotic nature of CTGF in these cells might contribute to the pathogenesis of BPD.…”

Regulation of TGF-β ligand and receptor expression in neonatal rat lungs exposed to chronic hypoxia

“…Although hyperoxia rather than hypoxia has been implicated in the pathophysiology of BPD, similar morphologic characteristics (i.e., inhibition of alveolarization) have been reported on pathological examination of lung sections from BPD patients, and it remains to be elucidated whether early hypoxia indeed represents an initial trigger for disease onset (14,17,23). Whereas TGF-␤ has been implicated in the pathogenesis of BPD before, a paucity of work exists in this field (28). Further investigations addressing specific regulatory mechanisms, as well as elucidation of the various downstream mediators of TGF-␤ signaling, may help to address the different phenotypes associated with increased TGF-␤ activity, both developmentally and with exposure to hypoxia.…”

“…During alveologenesis, close interactions of proliferating and differentiating epithelial cells with their surrounding endothelial cells are required for the subsequent proper formation of alveoli. It follows that, in the case of deficient or improper angiogenesis, the formation of alveoli is also inhibited, a mechanism that has been suggested to contribute to diseases such as bronchopulmonary dysplasia (BPD) or emphysema (14,28). In this respect, it has recently been shown that T␤RI receptor expression is a major regulator of vascular development.…”