糖皮质激素敏感性降低的分子机制研究进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

王圆方 ,  林江涛

中日友好医院呼吸与危重症医学科（北京 100029）;

Corresponding author：

林江涛, Email: jiangtao_l@263.net

Keywords：

DOI：

10.7507/1671-6205.201801028

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Citation： 王圆方, 林江涛. 糖皮质激素敏感性降低的分子机制研究进展. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(4): 426-429. doi: 10.7507/1671-6205.201801028 Copy

1.	Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med, 2005, 353(16):1711-1723.
2.	Morrison N, Harrap SB, Arriza JL, et al. Regional chromosomal assignment of the human mineralocorticoid receptor gene to 4q31.1. Hum Genet, 1990, 85(1):130-132.
3.	Hollenberg SM, Evans RM. Multiple and cooperative trans-activation domains of the human glucocorticoid receptor. Cell, 1988, 55(5):899-906.
4.	Biddie SC, Conway-Campbell BL, Lightman SL. Dynamic regulation of glucocorticoid signalling in health and disease. Rheumatology (Oxford), 2012, 51(3):403-412.
5.	Vazquez-Tello A, Semlali A, Chakir J, et al. Induction of glucocorticoid receptor‐β expression in epithelial cells of asthmatic airways by T-helper type 17 cytokines. Clin Exp Allergy, 2010, 40(9):1312-1322.
6.	Hillmann AG, Ramdas J, Multanen K, et al. Glucocorticoid receptor gene mutations in leukemic cells acquired in vitro and in vivo. Cancer Res, 2000, 60(7):2056-2062.
7.	Schaaf MJM, Cidlowski JA. AUUUA motifs in the 3′UTR of human glucocorticoid receptor α and β mRNA destabilize mRNA and decrease receptor protein expression. Steroids, 2002, 67(7):627-636.
8.	Wallace AD, Cao Y, Chandramouleeswaran S, et al. Lysine 419 targets human glucocorticoid receptor for proteasomal degradation. Steroids, 2010, 75(12):1016-1023.
9.	Breslin MB, Geng CD, Vedeckis WV. Multiple promoters exist in the human GR gene, one of which is activated by glucocorticoids. Mol Endocrinol, 2001, 15(8):1381-1395.
10.	Tissing WJ, Meijerink JP, Brinkhof B, et al. Glucocorticoid-induced glucocorticoid-receptor expression and promoter usage is not linked to glucocorticoid resistance in childhood ALL. Blood, 2006, 108(3):1045-1049.
11.	Gross KL, Lu NZ, Cidlowski JA. Molecular mechanisms regulating glucocorticoid sensitivity and resistance. Mol Cell Endocrinol, 2009, 300(1-2):7-16.
12.	Yudt MR, Cidlowski JA. Molecular identification and characterization of a and b forms of the glucocorticoid receptor. Mol Endocrinol, 2001, 15(7): 1093-1103.
13.	Geng CD, Pedersen B, Nunez BS, et al. Human glucocorticoid receptor alpha transcript splice variants with exon 2 deletions: evidence for tissue- and cell type-specific functions. Biochemistry, 2005, 44(20):7395-7405.
14.	Lu NZ, Cidlowski JA. Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Mol Cell, 2005, 18(3):331-342.
15.	Turner JD, Schote AB, Keipes M, et al. A new transcript splice variant of the human glucocorticoid receptor: identification and tissue distribution of hGR Delta 313-338, an alternative exon 2 transactivation domain isoform. Ann N Y Acad Sci, 2007, 1095(1):334-341.
16.	Hollenberg SM, Weinberger C, Ong ES, et al. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature, 1985, 318(6047):635-641.
17.	Presul E, Schmidt S, Kofler R, et al. Identification, tissue expression, and glucocorticoid responsiveness of alternative first exons of the human glucocorticoid receptor. J Mol Endocrinol, 2007, 38(1-2):79-90.
18.	Turner JD, Muller CP. Structure of the glucocorticoid receptor (NR3C1) gene 5′ untranslated region: identification, and tissue distribution of multiple new human exon 1. J Mol Endocrinol, 2005, 35(2):283-292.
19.	Yudt MR, Jewell CM, Bienstock RJ, et al. Molecular origins for the dominant negative function of human glucocorticoid receptor beta. Mol Cell Biol, 2003, 23(12):4319-4330.
20.	Oakley RH, Jewell CM, Yudt MR, et al. The dominant negative activity of the human glucocorticoid receptor beta isoform. Specificity and mechanisms of action. J Biol Chem, 1999, 274(39):27857-27866.
21.	Lewis-Tuffin LJ, Jewell CM, Bienstock RJ, et al. Human glucocorticoid receptor beta binds RU-486 and is transcriptionally active. Mol Cell Biol, 2007, 27(6):2266-2282.
22.	Kelly A, Bowen H, Jee YK, et al. The glucocorticoid receptor β isoform can mediate transcriptional repression by recruiting histone deacetylases. J Allergy Clin Immunol, 2008, 121(1):203-208.
23.	Pujols L, Mullol J, Roca-Ferrer J, et al. Expression of glucocorticoid receptor alpha- and beta-isoforms in human cells and tissues. Am J Physiol Cell Physiol, 2002, 283(4):1324-1331.
24.	Koga Y, Matsuzaki AA, Hattori H, et al. Differential mRNA expression of glucocorticoid receptor alpha and beta is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children. Pediatr Blood Cancer, 2005, 45(2):121-127.
25.	朱琦, 程毅敏, 叶为德, 等. 特发性血小板减少性紫癜患者激素敏感性与糖皮质激素受体亚型的关系研究. 血栓与止血学, 2007, 13(4):166-168.
26.	Haarman EG, Kaspers GJ, Pieters R, et al. Glucocorticoid receptor alpha, beta and gamma expression vs in vitro glucocorticod resistance in childhood leukemia. Leukemia, 2004, 18(3):530-537.
27.	Tissing WJ, Lauten M, Meijerink JP, et al. Expression of the glucocorticoid receptor and its isoforms in relation to glucocorticoid resistance in childhood acute lymphocytic leukemia. Haematologica, 2005, 51(90):1279-1281.
28.	Koper JW, Stolk RP, Lange PD, et al. Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance. Hum Genet, 1997, 99(5):663-668.
29.	Kojika S, Sugita K, Inukai T, et al. Mechanisms of glucocorticoid resistance in human leukemic cells: implication of abnormal 90 and 70 kDa heat shock proteins. Leukemia, 1996, 10(6):994-999.
30.	钱小顺, 朱元珏, 许文兵,等. 糖皮质激素敏感型、依赖型和抵抗型哮喘患者外周血单个核细胞中糖皮质激素受体和热休克蛋白 90 mRNA 表达的研究. 中华医学杂志, 2001, 114(10):43-46.
31.	Matysiak M, Makosa B, Walczak A, et al. Patients with multiple sclerosis resisted to glucocorticoid therapy: abnormal expression of heat-shock protein 90 in glucocorticoid receptor complex. Mult Scler, 2008, 14(7):919-926.
32.	Ouyang J, Jiang T, Tan M, et al. Abnormal expression and distribution of heat shock protein 90: potential etiologic immunoendocrine mechanism of glucocorticoid resistance in idiopathic nephrotic syndrome.. Clin Vaccine Immunol, 2006, 13(4):496-500.
33.	Tissing WJ, Meijerink JP, den Boer ML, et al. mRNA expression levels of (co)chaperone molecules of the glucocorticoid receptor are not involved in glucocorticoid resistance in pediatric ALL. Leukemia, 2005, 19(5):727-733.
34.	Denny WB, Prapapanich V, Smith DF, et al. Structure-function analysis of squirrel monkey FK506-binding protein 51, a potent inhibitor of glucocorticoid receptor activity. Endocrinology, 2005, 146(7):3194-3201.
35.	Galliher-Beckley AJ, Cidlowski JA. Emerging roles of glucocorticoid receptor phosphorylation in modulating glucocorticoid hormone action in health and disease. IUBMB Life, 2009, 61(10):979-986.
36.	Barnes PJ. Mechanisms and resistance in glucocorticoid control of inflammation. J Steroid Biochem Mol Biol, 2010, 120(2-3):76-85.
37.	Vrugt B, Wilson S, Bron A, et al. Low‐dose methotrexate treatment in severe glucocorticoid‐dependent asthma: effect on mucosal inflammation and in vitro sensitivity to glucocorticoids of mitogen‐induced T‐cell proliferation. Eur Respir J, 2000, 15(3):478-485.
38.	Hao M, Lin J, Shu J, et al. Clarithromycin might attenuate the airway inflammation of smoke-exposed asthmatic mice via affecting HDAC2. J Thorac Dis, 2015, 7(7):1189-1197.
39.	李雯, 林江涛, 孙力超, 等. SB203580 对烟雾暴露的哮喘大鼠的影响. 国际呼吸杂志, 2012, 32(20):399-402.
40.	Luo Q, Lin J, Zhang L, et al. The anti-malaria drug artesunate inhibits cigarette smoke and ovalbumin concurrent exposure-induced airway inflammation and might reverse glucocorticoid insensitivity. Int Immunopharmacol, 2015, 29(2):235-245.

1. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med, 2005, 353(16):1711-1723.
2. Morrison N, Harrap SB, Arriza JL, et al. Regional chromosomal assignment of the human mineralocorticoid receptor gene to 4q31.1. Hum Genet, 1990, 85(1):130-132.
3. Hollenberg SM, Evans RM. Multiple and cooperative trans-activation domains of the human glucocorticoid receptor. Cell, 1988, 55(5):899-906.
4. Biddie SC, Conway-Campbell BL, Lightman SL. Dynamic regulation of glucocorticoid signalling in health and disease. Rheumatology (Oxford), 2012, 51(3):403-412.
5. Vazquez-Tello A, Semlali A, Chakir J, et al. Induction of glucocorticoid receptor‐β expression in epithelial cells of asthmatic airways by T-helper type 17 cytokines. Clin Exp Allergy, 2010, 40(9):1312-1322.
6. Hillmann AG, Ramdas J, Multanen K, et al. Glucocorticoid receptor gene mutations in leukemic cells acquired in vitro and in vivo. Cancer Res, 2000, 60(7):2056-2062.
7. Schaaf MJM, Cidlowski JA. AUUUA motifs in the 3′UTR of human glucocorticoid receptor α and β mRNA destabilize mRNA and decrease receptor protein expression. Steroids, 2002, 67(7):627-636.
8. Wallace AD, Cao Y, Chandramouleeswaran S, et al. Lysine 419 targets human glucocorticoid receptor for proteasomal degradation. Steroids, 2010, 75(12):1016-1023.
9. Breslin MB, Geng CD, Vedeckis WV. Multiple promoters exist in the human GR gene, one of which is activated by glucocorticoids. Mol Endocrinol, 2001, 15(8):1381-1395.
10. Tissing WJ, Meijerink JP, Brinkhof B, et al. Glucocorticoid-induced glucocorticoid-receptor expression and promoter usage is not linked to glucocorticoid resistance in childhood ALL. Blood, 2006, 108(3):1045-1049.
11. Gross KL, Lu NZ, Cidlowski JA. Molecular mechanisms regulating glucocorticoid sensitivity and resistance. Mol Cell Endocrinol, 2009, 300(1-2):7-16.
12. Yudt MR, Cidlowski JA. Molecular identification and characterization of a and b forms of the glucocorticoid receptor. Mol Endocrinol, 2001, 15(7): 1093-1103.
13. Geng CD, Pedersen B, Nunez BS, et al. Human glucocorticoid receptor alpha transcript splice variants with exon 2 deletions: evidence for tissue- and cell type-specific functions. Biochemistry, 2005, 44(20):7395-7405.
14. Lu NZ, Cidlowski JA. Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Mol Cell, 2005, 18(3):331-342.
15. Turner JD, Schote AB, Keipes M, et al. A new transcript splice variant of the human glucocorticoid receptor: identification and tissue distribution of hGR Delta 313-338, an alternative exon 2 transactivation domain isoform. Ann N Y Acad Sci, 2007, 1095(1):334-341.
16. Hollenberg SM, Weinberger C, Ong ES, et al. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature, 1985, 318(6047):635-641.
17. Presul E, Schmidt S, Kofler R, et al. Identification, tissue expression, and glucocorticoid responsiveness of alternative first exons of the human glucocorticoid receptor. J Mol Endocrinol, 2007, 38(1-2):79-90.
18. Turner JD, Muller CP. Structure of the glucocorticoid receptor (NR3C1) gene 5′ untranslated region: identification, and tissue distribution of multiple new human exon 1. J Mol Endocrinol, 2005, 35(2):283-292.
19. Yudt MR, Jewell CM, Bienstock RJ, et al. Molecular origins for the dominant negative function of human glucocorticoid receptor beta. Mol Cell Biol, 2003, 23(12):4319-4330.
20. Oakley RH, Jewell CM, Yudt MR, et al. The dominant negative activity of the human glucocorticoid receptor beta isoform. Specificity and mechanisms of action. J Biol Chem, 1999, 274(39):27857-27866.
21. Lewis-Tuffin LJ, Jewell CM, Bienstock RJ, et al. Human glucocorticoid receptor beta binds RU-486 and is transcriptionally active. Mol Cell Biol, 2007, 27(6):2266-2282.
22. Kelly A, Bowen H, Jee YK, et al. The glucocorticoid receptor β isoform can mediate transcriptional repression by recruiting histone deacetylases. J Allergy Clin Immunol, 2008, 121(1):203-208.
23. Pujols L, Mullol J, Roca-Ferrer J, et al. Expression of glucocorticoid receptor alpha- and beta-isoforms in human cells and tissues. Am J Physiol Cell Physiol, 2002, 283(4):1324-1331.
24. Koga Y, Matsuzaki AA, Hattori H, et al. Differential mRNA expression of glucocorticoid receptor alpha and beta is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children. Pediatr Blood Cancer, 2005, 45(2):121-127.
25. 朱琦, 程毅敏, 叶为德, 等. 特发性血小板减少性紫癜患者激素敏感性与糖皮质激素受体亚型的关系研究. 血栓与止血学, 2007, 13(4):166-168.
26. Haarman EG, Kaspers GJ, Pieters R, et al. Glucocorticoid receptor alpha, beta and gamma expression vs in vitro glucocorticod resistance in childhood leukemia. Leukemia, 2004, 18(3):530-537.
27. Tissing WJ, Lauten M, Meijerink JP, et al. Expression of the glucocorticoid receptor and its isoforms in relation to glucocorticoid resistance in childhood acute lymphocytic leukemia. Haematologica, 2005, 51(90):1279-1281.
28. Koper JW, Stolk RP, Lange PD, et al. Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance. Hum Genet, 1997, 99(5):663-668.
29. Kojika S, Sugita K, Inukai T, et al. Mechanisms of glucocorticoid resistance in human leukemic cells: implication of abnormal 90 and 70 kDa heat shock proteins. Leukemia, 1996, 10(6):994-999.
30. 钱小顺, 朱元珏, 许文兵,等. 糖皮质激素敏感型、依赖型和抵抗型哮喘患者外周血单个核细胞中糖皮质激素受体和热休克蛋白 90 mRNA 表达的研究. 中华医学杂志, 2001, 114(10):43-46.
31. Matysiak M, Makosa B, Walczak A, et al. Patients with multiple sclerosis resisted to glucocorticoid therapy: abnormal expression of heat-shock protein 90 in glucocorticoid receptor complex. Mult Scler, 2008, 14(7):919-926.
32. Ouyang J, Jiang T, Tan M, et al. Abnormal expression and distribution of heat shock protein 90: potential etiologic immunoendocrine mechanism of glucocorticoid resistance in idiopathic nephrotic syndrome.. Clin Vaccine Immunol, 2006, 13(4):496-500.
33. Tissing WJ, Meijerink JP, den Boer ML, et al. mRNA expression levels of (co)chaperone molecules of the glucocorticoid receptor are not involved in glucocorticoid resistance in pediatric ALL. Leukemia, 2005, 19(5):727-733.
34. Denny WB, Prapapanich V, Smith DF, et al. Structure-function analysis of squirrel monkey FK506-binding protein 51, a potent inhibitor of glucocorticoid receptor activity. Endocrinology, 2005, 146(7):3194-3201.
35. Galliher-Beckley AJ, Cidlowski JA. Emerging roles of glucocorticoid receptor phosphorylation in modulating glucocorticoid hormone action in health and disease. IUBMB Life, 2009, 61(10):979-986.
36. Barnes PJ. Mechanisms and resistance in glucocorticoid control of inflammation. J Steroid Biochem Mol Biol, 2010, 120(2-3):76-85.
37. Vrugt B, Wilson S, Bron A, et al. Low‐dose methotrexate treatment in severe glucocorticoid‐dependent asthma: effect on mucosal inflammation and in vitro sensitivity to glucocorticoids of mitogen‐induced T‐cell proliferation. Eur Respir J, 2000, 15(3):478-485.
38. Hao M, Lin J, Shu J, et al. Clarithromycin might attenuate the airway inflammation of smoke-exposed asthmatic mice via affecting HDAC2. J Thorac Dis, 2015, 7(7):1189-1197.
39. 李雯, 林江涛, 孙力超, 等. SB203580 对烟雾暴露的哮喘大鼠的影响. 国际呼吸杂志, 2012, 32(20):399-402.
40. Luo Q, Lin J, Zhang L, et al. The anti-malaria drug artesunate inhibits cigarette smoke and ovalbumin concurrent exposure-induced airway inflammation and might reverse glucocorticoid insensitivity. Int Immunopharmacol, 2015, 29(2):235-245.

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糖皮质激素敏感性降低的分子机制研究进展

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