Bronchopulmonary Dysplasia, Volume 240 (Lung Biology in by Steven H. Abman

By Steven H. Abman

Rising treatments for BPD - reminiscent of Inhaled Nitrous Oxide, diet A, Antioxidant options, and low-dose steroid remedy

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Expression of Bmp3, -4, -5, and -7 are detected in embryonic lung. BMP4 is an important BMP member that plays a key role in normal lung development. Addition of exogenous BMP4 to intact embryonic lung explant culture stimulates lung branching, as reported by us and other groups (120,121). 5 mouse lung endoderm cultured in Matrigel, addition of BMP4 inhibited epithelial growth induced by the morphogen FGF10 (85). 7-kb human SP-C promoter, causes abnormal lung morphogenesis with cystic terminal sacs (122).

Abnormal branching and poor alveolization are observed in mice deficient in EgfrÀ/À. Mechanical stretch–stimulated EGFR phosphorylation, at least in part, induces differentiation of fetal epithelial cells via EGFR activation of the ERK pathway. Blockade of the EGFR or ERK pathway by specific inhibitors decreased stretch-inducible Sp-C mRNA expression. Maybe EGFR is part of a mechanic stimulus signal sensor during fetal lung development (147). Aberrant expression of matrix metaloprotease proteins (MMPs) is also detected in EgfrÀ/À null mutant mice, which suggests that MMPs may be involved in EGFR-regulated lung growth (148).

Other Wnt/b-catenin pathway members, Tcf1, Lef1, Tcf3, Tcf4, sFrp1, sFrp2, and sFrp4, are also expressed in the primordial epithelium, alveolar epithelium, and adjacent mesenchyme in specific spatiotemporal patterns (140). In human fetal lung, nuclear b-catenin is present in pulmonary acinar buds (141). Null mutation of b-catenin in mice results in abnormal cystic structure formation in the lung and prenatal lethality. On the basis of molecular marker detection, the lungs are composed primarily of proximal airways, suggesting that b-catenin is one of the essential components to specify proximal-distal axis of the lung (139).

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