Recombinant osteopontin attenuates hyperoxia-induced acute lung injury through inhibiting nuclear factor kappa B and matrix metalloproteinases 2 and 9.

Xiangfeng Zhang; Fen Liu; Guangfa Zhu; Zengzhi Wang

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Recombinant osteopontin attenuates hyperoxia-induced acute lung injury through inhibiting nuclear factor kappa B and matrix metalloproteinases 2 and 9.

Author: Xiangfeng ZHANG ¹ ; Fen LIU ² ; Guangfa ZHU ³ ; Zengzhi WANG ³
Author Information

1. Department of Respiratory Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China. Email: xfzh20008@163.com.
2. Department of Epidemiology and Statistics, School of Public Health, Capital Medical University, Beijing 100069, China.
3. Department of Respiratory Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Publication Type:Journal Article
MeSH: Acute Lung Injury; genetics; metabolism; Animals; Hyperoxia; metabolism; physiopathology; Matrix Metalloproteinase 2; genetics; metabolism; Matrix Metalloproteinase 9; genetics; metabolism; Mice; NF-kappa B; genetics; metabolism; Osteopontin; genetics; metabolism; Tissue Inhibitor of Metalloproteinase-1; genetics; metabolism; Tissue Inhibitor of Metalloproteinase-2; genetics; metabolism
From: Chinese Medical Journal 2014;127(23):4025-4030
CountryChina
Language:English
Abstract:
BACKGROUNDExposure of adult mice to more than 95% O2 produces a lethal injury by 72 hours. Nuclear factor kappa B (NF-κB) is a transcriptional factor that plays a key role in the modulation of cytokine networks during hyperoxia-induced acute lung injury (ALI). Osteopontin (OPN) is a phosphorylated glycoprotein produced principally by macrophages. Studies have reported that exogenous OPN can maintain the integrity of the cerebral microvascular basement membrane and reduce brain damage through inhibiting NF-κB activities in the brain after subarachnoid hemorrhage. However, it is not clear whether OPN can reduce lung injury during ALI by inhibiting transcriptional signal pathways of NF-κB and consequent inhibition of inflammatory cytokines. Thus we examined the effects and mechanisms of recombinant OPN (r-OPN) on ALI.
METHODSNinety-six mice were randomly divided into phosphate buffered saline (PBS) and r-OPN groups. Mice were put in an oxygen chamber (>95% O2) and assessed for lung injury at 24, 48, and 72 hours. Expressions of NF-κB, matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), and tissue inhibitors of MMP-2 and MMP-9 (TIMP-1, TIMP-2) mRNA in lungs were examined with RT-PCR. Expression and distribution of NF-κB protein in lungs were measured with immunohistochemistry.
RESULTSExposure to hyperoxia for 72 hours induced more severe lung injury in the PBS group compared with the r-OPN group. Expression of NF-κB mRNA in the PBS group exposed to hyperoxia for 48 and 72 hours was significantly higher than the r-OPN group (P < 0.05). With 72-hour exposure, expression of TIMP-1 mRNA in the r-OPN group was significantly higher than that of the PBS group (P < 0.05). Expression of TIMP-2 mRNA in the r-OPN group at 48 and 72 hours was significantly higher than those in the PBS group (P < 0.05). After 72-hour exposure, expression of NF-κB protein in airway epithelium in the PBS group was significantly higher than that in the r-OPN group (P < 0.05).
CONCLUSIONr-OPN can inhibit the release and activation of MMPs through inhibition of the expression of NF-κB and promotion of the expression of TIMPs, and alleviate hyperoxia-induced ALI.