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Neonatal CD44 Null Mice Are Protected From Hypoxia‐Induced Pulmonary Hypertension and Decreased Alveolarization, and Have Defects In TGFβ and ERK Signaling
Author(s) -
Savani Rashmin C.,
Wang Lin,
Williams Olatunji W.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.31.10
Subject(s) - hypoxia (environmental) , cd44 , medicine , endocrinology , mapk/erk pathway , bronchopulmonary dysplasia , phosphorylation , pulmonary hypertension , transforming growth factor , biology , chemistry , microbiology and biotechnology , oxygen , cell , organic chemistry , pregnancy , genetics , gestational age
Impaired neonatal vascular and alveolar development, and elevated TGFβ contribute to pulmonary hypertension (PH) and bronchopulmonary dysplasia (BPD). Since the hyaluronan receptor CD44 regulates TGFβ signaling, we examined the effects of hypoxia (12% vs. 21% O 2 ) from birth to postnatal day (PN) 14 in neonatal CD44 +/+ (WT) and CD44 −/− mice. At PN14, hypoxia‐exposed WT mice had right ventricular hypertrophy and decreased alveolarization. CD44 −/− mice exposed to hypoxia were completely protected from these changes. Hypoxia‐exposed WT lungs had increased active TGFβ and phospho‐Smad2 as compared to room air (RA) controls. Surprisingly, lungs from RA CD44 −/− mice had elevated active TGFβ and phospho‐Smad2 at baseline and these were not altered by hypoxia. Compared to lungs from hypoxia WT mice, lungs from hypoxia CD44 −/− mice had impaired ERK1/2 phosphorylation. After hypoxia, the TGFβ target gene alpha‐smooth muscle actin, was increased in WT, but not CD44 −/− mice. We conclude that hypoxia‐induced PH and decreased alveolarization require CD44 and ERK phosphorylation, and that Smad2 phosphorylation is necessary but not sufficient for TGFβ signaling in this context. We speculate that CD44 may be a novel therapeutic target for PH and BPD.