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Query: UMLS:C0242706 (
hyperoxia
)
5,219
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Retinal vascular damages are the cardinal hallmarks of retinopathy of prematurity (ROP), a leading cause of vision impairment and blindness in childhood. Both angiogenesis and vasculogenesis are disrupted in the
hyperoxia
-induced vaso-obliteration phase, and recapitulated, although aberrantly, in the subsequent ischemia-induced neovessel formation phase of ROP. Yet, whereas the histopathological features of ROP are well characterized, many key modulators with a therapeutic potential remain unknown. The
CCN1
protein also known as cysteine-rich protein 61 (Cyr61) is a dynamically expressed, matricellular protein required for proper angiogenesis and vasculogenesis during development. The expression of
CCN1
becomes abnormally reduced during the hyperoxic and ischemic phases of ROP modeled in the mouse eye with oxygen-induced retinopathy (OIR). Lentivirus-mediated re-expression of
CCN1
enhanced physiological adaptation of the retinal vasculature to
hyperoxia
and reduced pathological angiogenesis following ischemia. Remarkably, injection into the vitreous of OIR mice of hematopoietic stem cells (HSCs) engineered to express
CCN1
harnessed ischemia-induced neovessel outgrowth without adversely affecting the physiological adaptation of retinal vessels to
hyperoxia
. In vitro exposure of HSCs to recombinant
CCN1
induced integrin-dependent cell adhesion, migration, and expression of specific endothelial cell markers as well as many components of the Wnt signaling pathway including Wnt ligands, their receptors, inhibitors, and downstream targets.
CCN1
-induced Wnt signaling mediated, at least in part, adhesion and endothelial differentiation of cultured HSCs, and inhibition of Wnt signaling interfered with normalization of the retinal vasculature induced by
CCN1
-primed HSCs in OIR mice. These newly identified functions of
CCN1
suggest its possible therapeutic utility in ischemic retinopathy.
...
PMID:The matricellular protein cysteine-rich protein 61 (CCN1/Cyr61) enhances physiological adaptation of retinal vessels and reduces pathological neovascularization associated with ischemic retinopathy. 2121 76
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.
...
PMID:Recombinant CCN1 prevents hyperoxia-induced lung injury in neonatal rats. 2870 May 67
