Abstract:
BACKGROUND:Bronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease of premature infants. Connective tissue growth factor (CTGF) plays an important role in tissue development and remodeling. We have previously shown that targeted overexpression of CTGF in alveolar type II epithelial cells results in BPD-like pathology and activates β-catenin in neonatal mice. METHODS:Utilizing this transgenic mouse model and ICG001, a specific pharmacological inhibitor of β-catenin, we tested the hypothesis that β-catenin signaling mediates the effects of CTGF in the neonatal lung. Newborn CTGF mice and control littermates received ICG001 (10 mg/kg/dose) or placebo (dimethyl sulfoxide, equal volume) by daily i.p. injection from postnatal day 5 to 15. Alveolarization, vascular development, and pulmonary hypertension (PH) were analyzed. RESULTS:Administration of ICG001 significantly downregulated expression of cyclin D1, collagen 1a1, and fibronectin, which are the known target genes of β-catenin signaling in CTGF lungs. Inhibition of β-catenin signaling improved alveolar and vascular development and decreased pulmonary vascular remodeling. More importantly, the improved vascular development and vascular remodeling led to a decrease in PH. CONCLUSION:β-Catenin signaling mediates the autocrine and paracrine effects of CTGF in the neonatal lung. Inhibition of CTGF-β-catenin signaling may provide a novel therapy for BPD.
journal_name
Pediatr Resjournal_title
Pediatric researchauthors
Rong M,Chen S,Zambrano R,Duncan MR,Grotendorst G,Wu Sdoi
10.1038/pr.2016.52subject
Has Abstractpub_date
2016-07-01 00:00:00pages
136-44issue
1eissn
0031-3998issn
1530-0447pii
pr201652journal_volume
80pub_type
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journal_title:Pediatric research
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journal_title:Pediatric research
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pub_type: 评论,杂志文章
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journal_title:Pediatric research
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doi:10.1203/00006450-197504000-00002
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journal_title:Pediatric research
pub_type: 杂志文章
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journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199108000-00005
更新日期:1991-08-01 00:00:00
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journal_title:Pediatric research
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pub_type: 杂志文章
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更新日期:2004-05-01 00:00:00
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journal_title:Pediatric research
pub_type: 临床试验,杂志文章
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更新日期:2015-03-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章
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更新日期:2002-12-01 00:00:00