Recombinant CCN1 prevents hyperoxia-induced lung injury in neonatal rats

Ruben Vaidya, Ronald Zambrano, Julia K. Hummler, Shihua Luo, Matthew R. Duncan, Karen Young, Lester F. Lau, Shu Wu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

BackgroundCystein-rich protein 61 (Cyr61/CCN1) is a member of the CCN family of matricellular proteins that has an important role in tissue development and remodeling. However, the role of CCN1 in the pathogenesis of bronchopulmonary dysplasia (BPD) is unknown. Accordingly, we have investigated the effects of CCN1 on a hyperoxia-induced lung injury model in neonatal rats.MethodsIn experiment 1, newborn rats were randomized to room air (RA) or 85% oxygen (O 2) for 7 or 14 days, and we assessed the expression of CCN1. In experiment 2, rat pups were exposed to RA or O 2 and received placebo or recombinant CCN1 by daily intraperitoneal injection for 10 days. The effects of CCN1 on hyperoxia-induced lung inflammation, alveolar and vascular development, vascular remodeling, and right ventricular hypertrophy (RVH) were observed.ResultsIn experiment 1, hyperoxia downregulated CCN1 expression. In experiment 2, treatment with recombinant CCN1 significantly decreased macrophage and neutrophil infiltration, reduced inflammasome activation, increased alveolar and vascular development, and reduced vascular remodeling and RVH in the hyperoxic animals.ConclusionThese results demonstrate that hyperoxia-induced lung injury is associated with downregulated basal CCN1 expression, and treatment with CCN1 can largely reverse hyperoxic injury.

Original languageEnglish (US)
Pages (from-to)863-871
Number of pages9
JournalPediatric Research
Volume82
Issue number5
DOIs
StatePublished - Nov 1 2017

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Hyperoxia
Lung Injury
Right Ventricular Hypertrophy
CCN Intercellular Signaling Proteins
Blood Vessels
Down-Regulation
Air
Inflammasomes
Bronchopulmonary Dysplasia
Neutrophil Infiltration
Intraperitoneal Injections
Pneumonia
Macrophages
Placebos
Oxygen
Wounds and Injuries
Therapeutics
Proteins
Vascular Remodeling

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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Recombinant CCN1 prevents hyperoxia-induced lung injury in neonatal rats. / Vaidya, Ruben; Zambrano, Ronald; Hummler, Julia K.; Luo, Shihua; Duncan, Matthew R.; Young, Karen; Lau, Lester F.; Wu, Shu.

In: Pediatric Research, Vol. 82, No. 5, 01.11.2017, p. 863-871.

Research output: Contribution to journalArticle

Vaidya, R, Zambrano, R, Hummler, JK, Luo, S, Duncan, MR, Young, K, Lau, LF & Wu, S 2017, 'Recombinant CCN1 prevents hyperoxia-induced lung injury in neonatal rats', Pediatric Research, vol. 82, no. 5, pp. 863-871. https://doi.org/10.1038/pr.2017.160
Vaidya, Ruben ; Zambrano, Ronald ; Hummler, Julia K. ; Luo, Shihua ; Duncan, Matthew R. ; Young, Karen ; Lau, Lester F. ; Wu, Shu. / Recombinant CCN1 prevents hyperoxia-induced lung injury in neonatal rats. In: Pediatric Research. 2017 ; Vol. 82, No. 5. pp. 863-871.
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