Role of matrix metalloproteinase-9 in neonatal lung development under hypoxic stress

Hypoxia is a condition associated with many pulmonary diseases and can induce tissue and vascular remodeling, which can result in many pathological conditions. Since Matrix Metalloproteinases (MMP) family can alter the components of the matrix and thus is an important facilitator of the remodeling process; we chose to study the impact of MMP-9, a member of the MMP family that has been shown to be involved in many hypoxia-induced diseases, in hypoxia-induced lung remodeling in immature mice. MMP - 9 knockout (KO) mice and FVB controls (background for MMP- 9 KO) were both ex- posed to either 11%O2 or room air from postnatal days 2 to 17. At P17, mice were sacrificed and lungs were processed for protein and histology. In hypoxia, the survival rate of MMP-9 KO mice was significantly lower than MMP-9 WT mice. MMP-9 KO mice that survived hypoxia exposure were significantly smaller than MMP-9 WT mice. Histology revealed that MMP-9 KO mice that survived hypoxia had increased muscularized vessels and larger alveolar diameter than MMP-9 WT mice. Protein analysis demonstrated significant changes in ECM and overall increased in MMP expression in MMP-9 KO mice compared to MMP-9 WT exposed to chronic hypoxia. Our study indicates that MMP-9 may play a critical role in hypoxia-induced tissue and vascular remodeling. Deletion of this protein results in increased mortality that may be associated with increased smooth muscle proliferation and increased alveolar diamete