Objective To investigate the dynamic expression of small ubiquitin-related modifiers-1 ( SUMO-1) in lung tissue in different phases of rat model of hypoxic pulmonary hypertension( HPH) .Methods Forty Wistar rats were randomly divided into 5 groups, and exposed to normoxia or to normobaric intermittent hypoxia for 3, 7, 14 or 21 days, respectively. Mean pulmonary arterial pressure( mPAP) , right ventricle hypertrophy index ( RVHI) , and the ratio of the vessel wall area to the total area( WA% ) were
measured. RT-PCR and in situ hybridization were used to determine the mRNA expression of SUMO-1.Immunohistochemistry and Western blot were used to determine the protein expression of SUMO-1. Results The hypoxic rats developed pulmonary vascular remodeling in pulmonary arterioles after 7 days of hypoxia,with WA% and mPAP significantly higher than those in the normal control. Pulmonary vascular remodeling aggravated with much higherWA% and mPAP afer 14 days of hypoxia, and reached the peak afer 21 days of hypoxia. SUMO-1 mRNA and protein expression markedly increased after 3 days of hypoxia, and reached peak after 14 days. After 21 days of hypoxia, SUMO-1 mRNA expression weakened but still higher than that in the normal control ( P lt; 0. 05) , and SUMO-1 protein expression remained stable. SUMO-1 mRNA and protein expression were positively correlated with mPAP, WA% and RVHI( all P lt; 0. 01) . Conclusion SUMO-1 is transcriptionally induced in lung tissue under chronic hypoxia, and thus involves in the pathogenesis of HPH.
Citation：
TIAN Hua,DAI Aiguo,FU Daiyan,TAN Shuangxiang,HU Ruicheng,ZHU Liming. The Role of Small Ubiquitin-Related Modifiers-1 in the Pathogenesis of Hypoxic Pumonary Hypertension in Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(1): 48-52. doi:
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Copyright © the editorial department of Chinese Journal of Respiratory and Critical Care Medicine of West China Medical Publisher. All rights reserved
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田华,戴爱国.HIF-1a可逆性SUMO化修饰.中国生物化学与分子生物学报,2009,25:1-6.
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Carbia-Nagashima A,Gerez J,Perez-Castro C,et al.RSUME,a small RWD-containing protein,enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia.Cell,2007,131:309-323.
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Bae SH,Jeong JW,Park JA,et al.Sumoylation increases HIF-1alpha stability and its transcriptional activity.Biochem Biophys Res Commun,2004,324:394-400.
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李炽观,戴爱国,严鹏科.低氧诱导因子1在低氧致肺动脉平滑肌细胞增殖中的作用.中国病理生理杂志,2007,23: 1301-1305.
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Li QF,Dai AG.Differential expression of three hypoxia-inducible factor-alpha subunits in pulmonary arteries of rat with hypoxia-induced hypertension.Acta Biochim Biophys Sin (Shanghai).2005,37:665-672.
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Li QF,Dai AG.Hypoxia inducible factor-1 alpha correlates the expression of heme oxygenase 1 gene in pulmonary arteries of rat with hypoxia-induced pulmonary hypertension.Acta Biochim Biophys Sin (Shanghai),2004,36:133-140.
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Li QF,Dai AG.Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.Chin Med J (Engl),2004,117:1023-1028.
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Fu D,Dai A,Hu R,et al.Expression and role of factor inhibiting hypoxia-inducible factor-1 in pulmonary arteries of rat with hypoxia-induced hypertension.Acta Biochim Biophys Sin (Shanghai),2008,40:883-892.
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Stenmark KR,Davie NJ,Reeves JT,et al.Hypoxia,leukocytes,and the pulmonary circulation.J Appl Physiol,2005,98:715-721.
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- 1. 田华,戴爱国.HIF-1a可逆性SUMO化修饰.中国生物化学与分子生物学报,2009,25:1-6.
- 2. Bohren KM,Nadkarni V,Song JH,et al.A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus.J Biol Chem,2004,279:27233-27238.
- 3. Shao R,Zhang FP,Tian F,et al.Increase of SUMO-1 expression in response to hypoxia: direct interaction with HIF-1alpha in adult mouse brain and heart in vivo.FEBS Lett,2004,569:293-300.
- 4. Carbia-Nagashima A,Gerez J,Perez-Castro C,et al.RSUME,a small RWD-containing protein,enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia.Cell,2007,131:309-323.
- 5. Bae SH,Jeong JW,Park JA,et al.Sumoylation increases HIF-1alpha stability and its transcriptional activity.Biochem Biophys Res Commun,2004,324:394-400.
- 6. 李炽观,戴爱国,严鹏科.低氧诱导因子1在低氧致肺动脉平滑肌细胞增殖中的作用.中国病理生理杂志,2007,23: 1301-1305.
- 7. Li QF,Dai AG.Differential expression of three hypoxia-inducible factor-alpha subunits in pulmonary arteries of rat with hypoxia-induced hypertension.Acta Biochim Biophys Sin (Shanghai).2005,37:665-672.
- 8. Li QF,Dai AG.Hypoxia inducible factor-1 alpha correlates the expression of heme oxygenase 1 gene in pulmonary arteries of rat with hypoxia-induced pulmonary hypertension.Acta Biochim Biophys Sin (Shanghai),2004,36:133-140.
- 9. Li QF,Dai AG.Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.Chin Med J (Engl),2004,117:1023-1028.
- 10. Fu D,Dai A,Hu R,et al.Expression and role of factor inhibiting hypoxia-inducible factor-1 in pulmonary arteries of rat with hypoxia-induced hypertension.Acta Biochim Biophys Sin (Shanghai),2008,40:883-892.
- 11. Stenmark KR,Davie NJ,Reeves JT,et al.Hypoxia,leukocytes,and the pulmonary circulation.J Appl Physiol,2005,98:715-721.
