Thrombospondin-1 Airway Expression and Thrombospondin-1 Gene Variants Are Associated with Bronchopulmonary Dysplasia in Extremely Low-Birth-Weight Infants: A Pilot Study.

BACKGROUND: Thrombospondin-1 (TSP-1) is an extracellular glycoprotein that mediates the differentiation of pulmonary endothelial cells and specialized stem cells into alveolar epithelial lineage-specific cells during the repair phase after lung injury. Since bronchopulmonary dysplasia (BPD) involves the inhibition of lung development with altered lung structure and vasculature, differential expression of the THBS-1 gene may impact lung development and pulmonary endothelial cell repair and have an important role in BPD. METHODS: This prospective single-center cohort study included ELBW infants with and without BPD. DNA from buccal swabs underwent RT-PCR with TaqMan probes, and TSP-1 protein was measured in tracheal aspirates. Statistical analyses used Chi-square tests, Fisher's exact tests, Wilcoxon Rank Sum tests, and t-tests (p < 0.05). RESULTS: ELBW infants with BPD had significantly lower gestational ages and birth weights compared to those without BPD [25 (24,26) and 27 (25,28) weeks; median (IQR); p = 0.008] and [712 (155) and 820 (153) grams; mean (SD); p = 0.002], respectively. There were significant differences in the haplotype distributions of THBS1 variants rs2664139/rs1478604 (p = 0.006) and THBS1 variants rs1478605/rs1478604 (p = 0.008) between no-BPD and BPD groups. There were also significant differences in airway TSP-1 protein levels between moderate and severe BPD patients [(p = 0.02) (no BPD: 527 (114-1755); moderate BPD: 312 (262-641); and severe BPD 211: (117-352) ng/dL; median (IQR)]. CONCLUSIONS: Although no individual variants differed, two THBS1 haplotypes and early TSP-1 airway expression varied by BPD severity, suggesting a role for TSP-1 in lung development and BPD pathogenesis in ELBW infants.