Recombinant Osteopontin Attenuate Hyperoxia-induced Acute Lung Injury by Inhibiting Expressions of Nuclear Factor-κB and Matrix Metalloproteinase 2 and 9_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 ZhangXiangfeng ¹ , LiuFen ² , ZhuGuangfa ¹ , WangZengzhi ¹

1. Department of Respiratory Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China;
2. ;

Corresponding author：

ZhangXiangfeng, Email: xfzh20008@163.com

Keywords：

Osteopontin; Hyperoxia; Acute lung injury; Nuclear factor-κB; Matrixmetalloproteinse

DOI：

10.7507/1671-6205.2014089

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the role of osteopontin (OPN) in hyperoxia-induced acute lung injury and its relationship with nuclear factor-κB (NF-κB),matrix metalloproteinase 2 and 9 (MMP-2,MMP-9). Methods Ninety-six mice were randomly divided into a phosphate buffer solution intranasal inhalation group (PBS group) and a recombinant OPN intranasal inhalation group. The mice were exposed in sealed cages >95% oxygen for 24-72 hours to induce lung injury or room air as control. The severity of lung injury was evaluated. The expression of NF-κB,MMP-2,MMP-9,TIMP-1 and TIMP-2 mRNA in lung tissue at 24,48 and 72 hours under hyperoxia were examined by reverse transcript-polymerase chain reaction (RT-PCR). Immunohistochemistry (IHC) was performed for detection of NF-κB protein in lung tissue. Results PBS group mice developed more severe acute lung injury at 72 hours under hyperoxia.TIMP-1 and TIMP-2 mRNA expressions were significantly increased in r-OPN group than their matched PBS group when exposed to hyperoxia. IHC study showed higher expression of NF-κB protein in lung tissue of PBS group at 72 hours of hyperoxia. Conclusion OPN can protect against hyperoxia-induced lung injury by inhibiting the expressions of NF-κB,MMP-2 and MMP-9.

Citation： ZhangXiangfeng, LiuFen, ZhuGuangfa, WangZengzhi. Recombinant Osteopontin Attenuate Hyperoxia-induced Acute Lung Injury by Inhibiting Expressions of Nuclear Factor-κB and Matrix Metalloproteinase 2 and 9. Chinese Journal of Respiratory and Critical Care Medicine, 2014, 13(4): 364-369. doi: 10.7507/1671-6205.2014089 Copy

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16.	Guo H,Cai CQ,Schroeder RA,et al.Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages.J Immunol,2001,166:1079-1086.
17.	Minai-Tehrani A,Chang SH,Kwon JT,et al.Aerosol delivery of lentivirus-mediated O-glycosylation mutant osteopontin suppresses lung tumorigenesis in K-ras (LA1) mice.Cell Oncol (Dordr),2013,36:15-26.
18.	Matušan-Ilijaš K,Damante G,Fabbro D,et al.Osteopontin expression correlates with nuclear factor-κB activation and apoptosis downregulation in clear cell renal cell carcinoma.Pathol Res Pract,2011,207:104-110.
19.	Guo H,Cai CQ,Schroeder RA,et al.Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages.J Immunol,2001,166:1079-1086.
20.	张向峰,Hussein D.Foda.骨桥蛋白在高氧所致急性肺损伤中的作用及机理的初步探讨.中华结核和呼吸杂志,2006,29:385-389.

1. ARDS Definition Task Force,Ranieri VM,Rubenfeld GD,et al.Acute respiratory distress syndrome:the Berlin Definition.JAMA,2012,307:2526-2533.
2. Silversides JA,Ferguson ND.Clinical review:Acute respiratory distress syndrome-clinical ventilator management and adjunct therapy.Crit Care,2012,17:225.
3. Davey A,McAuley DF,O'Kane CM.Matrix metalloproteinases in acute lung injury:mediators of injury and drivers of repair. Eur Respir J,2011,38:959-970.
4. Rahman A,Fazal F.Blocking NF-κB:an inflammatory issue.Proc Am Thorac Soc,2011,8:497-503.
5. Suzuki H,Hasegawa Y,Ayer R,et al.Effects of recombinant osteopontin on blood-brain barrier disruption after subarachnoid hemorrhage in rats.Acta Neurochir Suppl,2011,111:231-236.
6. Suzuki H,Hasegawa Y,Kanamaru K,et al.Mechanisms of osteopontin-induced stabilization of blood-brain barrier disruption after subarachnoid hemorrhage in rats.Stroke,2010,41:1783-1790.
7. Barbera JA,Peinado VI,Santos S,et al,Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of smokers.Am J Respir Crit Care Med,2001,164:709-713.
8. Zhou X,Dai Q,Huang X.Neutrophils in acute lung injury.Front Biosci,2012,17:2278-2283.
9. 张向峰,丁少芳,高元明,等.多种基质金属蛋白酶在高氧所致急性肺损伤中的表达.中国危重病急救医学,2006,18:449-451.
10. Qiu Z,Hu J,Van den Steen PE,et al.Targeting matrix metalloproteinases in acute inflammatory shock syndromes.Comb Chem High Throughput Screen,2012,15:555-570.
11. O'Kane CM,McKeown SW,Perkins GD,et al.Salbutamol up-regulates matrix metalloproteinase-9 in the alveolar space in the acute respiratory distress syndrome.Crit Care Med,2009,37:2242-2249.
12. Tornatore L,Thotakura AK,Bennett J,et al.The nuclear factor kappa B signaling pathway:integrating metabolism with inflammation.Trends Cell Biol,2012,22:557-666.
13. Lai WW,Hsu SC,Chueh FS,et al.Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-κB and matrix metalloproteinase-2/-9 signaling pathways.Anticancer Res,2013,33:1941-1950.
14. Xue H,Sun K,Xie W,et al.Etanercept attenuates short-term cigarette-smoke-exposure-induced pulmonary arterial remodelling in rats by suppressing the activation of TNF-a/NF-kB signal and the activities of MMP-2 and MMP-9.Pulm Pharmacol Ther,2012,25:208-215.
15. Henke N,Schmidt-Ullrich R,Dechend R,et al.Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage.Circ Res,2007,101:268-276.
16. Guo H,Cai CQ,Schroeder RA,et al.Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages.J Immunol,2001,166:1079-1086.
17. Minai-Tehrani A,Chang SH,Kwon JT,et al.Aerosol delivery of lentivirus-mediated O-glycosylation mutant osteopontin suppresses lung tumorigenesis in K-ras (LA1) mice.Cell Oncol (Dordr),2013,36:15-26.
18. Matušan-Ilijaš K,Damante G,Fabbro D,et al.Osteopontin expression correlates with nuclear factor-κB activation and apoptosis downregulation in clear cell renal cell carcinoma.Pathol Res Pract,2011,207:104-110.
19. Guo H,Cai CQ,Schroeder RA,et al.Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages.J Immunol,2001,166:1079-1086.
20. 张向峰,Hussein D.Foda.骨桥蛋白在高氧所致急性肺损伤中的作用及机理的初步探讨.中华结核和呼吸杂志,2006,29:385-389.

Chinese Journal of Respiratory and Critical Care Medicine

Recombinant Osteopontin Attenuate Hyperoxia-induced Acute Lung Injury by Inhibiting Expressions of Nuclear Factor-κB and Matrix Metalloproteinase 2 and 9

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