IFN-γ and TNF-α Impair Lung Development by Upregulating SMAD7 to Inhibit TGF-β Signaling Pathway and ECM Dysregulation.

ABSTRACT: Inflammation plays a pivotal role in neonatal lung injury and is closely associated with the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants, although the underlying molecular mechanisms remain incompletely understood. Our study detected elevated serum levels of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in preterm neonates as early as postnatal day 1 among those who later developed moderate-to-severe BPD. In pulmonary fibroblasts, co-treatment. with IFN-γ and TNF-α significantly downregulated α-smooth muscle actin (α-SMA) and disrupted extracellular matrix (ECM) homeostasis, evidenced by reduced collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and elastin expression, but elevated fibronectin 1 (FN1) and matrix metalloproteinas

SUBMITTER: Liao X 

PROVIDER: S-EPMC12907279 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature