G 蛋白偶联雌激素受体信号通路与肺脏疾病_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

毛建军 ,  袁雅冬

河北医科大学第二医院呼吸与危重症医学科（河北石家庄 050000）;

Corresponding author：

袁雅冬, Email: yyd1108@126.com

Keywords：

DOI：

10.7507/1671-6205.201606040

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Citation： 毛建军, 袁雅冬. G 蛋白偶联雌激素受体信号通路与肺脏疾病. Chinese Journal of Respiratory and Critical Care Medicine, 2017, 16(3): 307-311. doi: 10.7507/1671-6205.201606040 Copy

1.	Prossnitz ER, Arterburn JB. International Union of Basic and Clinical Pharmacology. ⅩCⅦ. G protein-coupled estrogen receptor and its pharmacologic modulators. Pharmacol Rev, 2015, 67(3): 505-540.
2.	Prossnitz ER, Hathaway HJ. What have we learned about GPER function in physiology and disease from knockout mice?. J Steroid Biochem Mol Biol, 2015, 153: 114-126.
3.	Lappano R, Pisano A, Maggiolini M. GPER function in breast cancer: an overview. Front Endocrinol (Lausanne), 2014, 5: 66.
4.	Barton M, Prossnitz ER. Emerging roles of GPER in diabetes and atherosclerosis. Trends Endocrinol Metab, 2015, 26(4): 185-192.
5.	Pietras RJ, Szego CM. Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells. Nature, 1977, 265(5589): 69-72.
6.	Carmeci C, Thompson DA, Ring HZ, et al. Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer. Genomics, 1997, 45(3): 607-617.
7.	Rosano C, Lappano R, Santolla MF, et al. Recent advances in the rationale design of GPER ligands. Curr Med Chem, 2012, 19(36): 6199-6206.
8.	Cygankiewicz AI, Jacenik D, Krajewska WM. GPER receptor-the new player in estrogen signaling. Postepy Biochem, 2015, 61(1): 52-60.
9.	Kim MJ, Kim TH, Lee HH. G-protein coupled estrogen receptor (GPER/GPR30) and women’s health. J Menopausal Med, 2015, 21(2): 79-81.
10.	Filardo E, Quinn J, Pang Y, et al. Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membran. Endocrinology, 2007, 148(7): 3236-3245.
11.	Pupo M, Vivacqua A, Perrotta I, et al. The nuclear localization signal is required for nuclear GPER translocation and function in breast cancer-associated fibroblasts (CAFs). Mol Cell Endocrinol, 2013, 376(1-2): 23-32.
12.	Cheng SB, Dong J, Pang Y, et al. Anatomical location and redistribution of G protein-coupled estrogen receptor-1 during the estrus cycle in mouse kidney and specific binding to estrogens but not aldosterone. Mol Cell Endocrinol, 2014, 382(2): 950-959.
13.	Sharma G, Prossnitz ER. GPER/GPR30 knockout mice: effects of GPER on metabolism. Methods Mol Biol, 2016, 1366: 489-502.
14.	Sharma G, Hu C, Brigman JL, et al. GPER deficiency in male mice results in insulin resistance, dyslipidemia, and a proinflammatory state. Endocrinology, 2013, 154(11): 4136-4145.
15.	Zhu P, Yuen JM, Sham KW, et al. GPER mediates the inhibitory actions of estrogen on adipogenesis in 3T3-L1 cells through perturbation of mitotic clonal expansion. Gen Comp Endocrinol, 2013, 193: 19-26.
16.	Davis KE, Carstens EJ, Irani BG, et al. Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis. Horm Behav, 2014, 66(1): 196-207.
17.	Sharma G, Prossnitz ER. Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic β-cells. Endocrinology, 2011, 152(8): 3030-3039.
18.	Liu SH, Le May C, Wong WP, et al. Importance of extranuclear estrogen receptor-α and membrane G protein-coupled estrogen receptor in pancreatic islet survival. Diabetes, 2009, 58(10): 2292-2302.
19.	Wang C, Dehghani B, Magrisso I, et al. GPR30 contributes to estrogen-induced thymic atrophy. Mol Endocrinol, 2008, 22(3): 636-648.
20.	Cabas I, Rodenas MC, Abellán E, et al. Estrogen signaling through the G protein-coupled estrogen receptor regulates granulocyte activation in fish. J Immunol, 2013, 191(9): 4628-4639.
21.	Rettew JA, McCall SH, Marriott I. GPR30/GPER-1 mediates rapid decreases in TLR4 expression on murine macrophages. Mol Cell Endocrinol, 2010, 328(1-2): 87-92.
22.	Brunsing RL, Owens KS, Prossnitz ER. The G protein-coupled estrogen receptor (GPER) agonist G-1 expands the regulatory T-cell population under TH17-polarizing conditions. J Immunother, 2013, 36(3): 190-196.
23.	Kim MJ, Kim TH, Lee HH. G-protein coupled estrogen receptor (GPER/GPR30) and women’s health. J Menopausal Med, 2015, 21(2): 79-81.
24.	Pupo M, Pisano A, Abonante S, et al. GPER activates notch signaling in breast cancer cells and cancer-associated fibroblasts (CAFs). Int J Biochem Cell Biol, 2014, 46: 56-67.
25.	Li Y, Chen Y, Zhu ZX, et al. 4-Hydroxytamoxifen-stimulated processing of cyclinE is mediated via G protein-coupled receptor 30 (GPR30) and accompanied by enhanced migration in MCF-7 breast cancer cells. Toxicology, 2013, 309: 61-65.
26.	Girgert R, Emons G, Gründker C. 17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib. Oncol Rep, 2017, 37(2): 1212-1218.
27.	Yan Y, Jiang X, Zhao Y, et al. Role of GPER on proliferation, migration and invasion in ligand-independent manner in human ovarian cancer cell line SKOV3. Cell Biochem Funct, 2015, 33(8): 552-559.
28.	Feldman RD, Ding Q, Hussain Y, et al. Aldosterone mediates metastatic spread of renal cancer via the G protein-coupled estrogen receptor (GPER). FASEB J, 2016, 30(6): 2086-2096.
29.	Rudelius M, Rauert-Wunderlich H, Hartmann E, et al. The G protein-coupled estrogen receptor 1 (GPER-1) contributes to the proliferation and survival of mantle cell lymphoma cells. Haematologica, 2015, 100(11): e458-e461.
30.	Zhang Q, Wu YZ, Zhang YM, et al. Activation of G-protein coupled estrogen receptor inhibits the proliferation of cervical cancer cells via sustained activation of ERK1/2. Cell Biochem Funct, 2015, 33(3): 134-142.
31.	Mori T, Ito F, Matsushima H, et al. G protein-coupled estrogen receptor 1 agonist G-1 induces cell cycle arrest in the mitotic phase, leading to apoptosis in endometriosis. Fertil Steril, 2015, 103(5): 1228-1235.
32.	Huff MO, Todd SL, Smith AL, et al. Arsenite and cadmium activate MAPK/ERK via membrane estrogen receptors and g-protein coupled estrogen receptor signaling in human lung adenocarcinoma cells. Toxicol Sci, 2016, 152(1): 62-71.
33.	Liu CY, Liao YD, Fan S, et al. G protein-coupled estrogen receptor (GPER) mediates NSCLC progression induced by 17β-estradiol (E ₂) and selective agonist G1. Med Oncol, 2015, 32(4): 104.
34.	Zhang KS, Chen HQ, Chen YS, et al. Bisphenol A stimulates human lung cancer cell migration via upregulation of matrix metalloproteinases by GPER/EGFR/ERK1/2 signal pathway. Biomed Pharmacother, 2014, 68(8): 1037-1043.
35.	Zhu G, Huang Y, Wu C, et al. Activation of G-protein-coupled estrogen receptor inhibits the migration of human nonsmall cell lung cancer cells via IKK-β/NF-κB signals. DNA Cell Biol, 2016, 35(8): 434-442.
36.	Gui Y, Shi Z, Wang Z, et al. The GPER agonist G-1 induces mitotic arrest and apoptosis in human vascular smooth muscle cells independent of GPER. J Cell Physiol, 2015, 230(4): 885-895.
37.	The ENFUMOSA Study Group. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. European Network for Understanding Mechanisms of Severe Asthma. Eur Respir, 2003, 22(3): 470-477.
38.	Cai Y, Zhou J, Webb DC. Estrogen stimulates Th2 cytokine production and regulates the compartmentalisation of eosinophils during allergen challenge in a mouse model of asthma. Int Arch Allergy Immunol, 2012, 158(3): 252-260.
39.	Tamaki M, Konno Y, Kobayashi Y, et al. Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils. Immunol Lett, 2014, 160(1): 72-78.
40.	Itoga M, Konno Y, Moritoki Y, et al. G-protein-coupled estrogen receptor agonist suppresses airway inflammation in a mouse model of asthma through IL-10. PLoS One, 2015, 10(3): e0123210.
41.	Hao Y, Chow AW, Yip WC, et al. G protein-coupled estrogen receptor inhibits the P2Y receptor-mediated Ca²⁺ signaling pathway in human airway epithelia. Pflugers Arch, 2016, 468(8): 1489-1503.
42.	Austin ED, Lahm T, West J, et al. Gender, sex hormones and pulmonary hypertension. Pulm Circ, 2013, 3(2): 294-314.
43.	Huang S, Chen P, Shui X, et al. Baicalin attenuates transforming growth factor-β1-induced human pulmonary artery smooth muscle cell proliferation and phenotypic switch by inhibiting hypoxia inducible factor-1α and aryl hydrocarbon receptor expression. J Pharm Pharmacol, 2014, 66(10): 1469-1477.
44.	Fernandez RA, Wan J, Song S, et al. Upregulated expression of STIM2, TRPC6, and Orai2 contributes to the transition of pulmonary arterial smooth muscle cells from a contractile to proliferative phenotype. Am J Physiol Cell Physiol, 2015 308(8): C581-C593.
45.	Coll-Bonfill N, Musri MM, Ivo V, et al. Transdifferentiation of endothelial cells to smooth muscle cells play an important role in vascular remodelling. Am J Stem Cells, 2015, 4(1): 13-21.
46.	Lindsey SH, da Silva AS, Silva MS, et al. Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation. Am J Physiol Endocrinol Metab, 2013, 305: E113-E118.
47.	Koganti S, Snyder R, Gumaste U, et al. 2-methoxyestradiol binding of GPR30 down-regulates angiotensin AT1 receptor. Eur J Pharmacol, 2014, 723: 131-140.
48.	Han G, White RE. G-protein-coupled estrogen receptor as a new therapeutic target for treating coronary artery disease. World J Cardiol, 2014, 6(6): 367-375.
49.	Zhao Z, Wang H, Jessup JA, et al. Role of estrogen in diastolic dysfunction. Am J Physiol Heart Circ Physiol, 2014, 306(5): H628-H640.
50.	Reslan OM, Yin Z, do Nascimento GR, et al. Subtype-specific estrogen receptor-mediated vasodilator activity in the cephalic, thoracic, and abdominal vasculature of female rat. J Cardiovasc Pharmacol, 2013, 62(1): 26-40.
51.	Alencar AK, Montes GC, Montagnoli T, et al. Activation of GPER ameliorates experimental pulmonary hypertension in male rats. Eur J Pharm Sci, 2017, 97: 208-217.

1. Prossnitz ER, Arterburn JB. International Union of Basic and Clinical Pharmacology. ⅩCⅦ. G protein-coupled estrogen receptor and its pharmacologic modulators. Pharmacol Rev, 2015, 67(3): 505-540.
2. Prossnitz ER, Hathaway HJ. What have we learned about GPER function in physiology and disease from knockout mice?. J Steroid Biochem Mol Biol, 2015, 153: 114-126.
3. Lappano R, Pisano A, Maggiolini M. GPER function in breast cancer: an overview. Front Endocrinol (Lausanne), 2014, 5: 66.
4. Barton M, Prossnitz ER. Emerging roles of GPER in diabetes and atherosclerosis. Trends Endocrinol Metab, 2015, 26(4): 185-192.
5. Pietras RJ, Szego CM. Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells. Nature, 1977, 265(5589): 69-72.
6. Carmeci C, Thompson DA, Ring HZ, et al. Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer. Genomics, 1997, 45(3): 607-617.
7. Rosano C, Lappano R, Santolla MF, et al. Recent advances in the rationale design of GPER ligands. Curr Med Chem, 2012, 19(36): 6199-6206.
8. Cygankiewicz AI, Jacenik D, Krajewska WM. GPER receptor-the new player in estrogen signaling. Postepy Biochem, 2015, 61(1): 52-60.
9. Kim MJ, Kim TH, Lee HH. G-protein coupled estrogen receptor (GPER/GPR30) and women’s health. J Menopausal Med, 2015, 21(2): 79-81.
10. Filardo E, Quinn J, Pang Y, et al. Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membran. Endocrinology, 2007, 148(7): 3236-3245.
11. Pupo M, Vivacqua A, Perrotta I, et al. The nuclear localization signal is required for nuclear GPER translocation and function in breast cancer-associated fibroblasts (CAFs). Mol Cell Endocrinol, 2013, 376(1-2): 23-32.
12. Cheng SB, Dong J, Pang Y, et al. Anatomical location and redistribution of G protein-coupled estrogen receptor-1 during the estrus cycle in mouse kidney and specific binding to estrogens but not aldosterone. Mol Cell Endocrinol, 2014, 382(2): 950-959.
13. Sharma G, Prossnitz ER. GPER/GPR30 knockout mice: effects of GPER on metabolism. Methods Mol Biol, 2016, 1366: 489-502.
14. Sharma G, Hu C, Brigman JL, et al. GPER deficiency in male mice results in insulin resistance, dyslipidemia, and a proinflammatory state. Endocrinology, 2013, 154(11): 4136-4145.
15. Zhu P, Yuen JM, Sham KW, et al. GPER mediates the inhibitory actions of estrogen on adipogenesis in 3T3-L1 cells through perturbation of mitotic clonal expansion. Gen Comp Endocrinol, 2013, 193: 19-26.
16. Davis KE, Carstens EJ, Irani BG, et al. Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis. Horm Behav, 2014, 66(1): 196-207.
17. Sharma G, Prossnitz ER. Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic β-cells. Endocrinology, 2011, 152(8): 3030-3039.
18. Liu SH, Le May C, Wong WP, et al. Importance of extranuclear estrogen receptor-α and membrane G protein-coupled estrogen receptor in pancreatic islet survival. Diabetes, 2009, 58(10): 2292-2302.
19. Wang C, Dehghani B, Magrisso I, et al. GPR30 contributes to estrogen-induced thymic atrophy. Mol Endocrinol, 2008, 22(3): 636-648.
20. Cabas I, Rodenas MC, Abellán E, et al. Estrogen signaling through the G protein-coupled estrogen receptor regulates granulocyte activation in fish. J Immunol, 2013, 191(9): 4628-4639.
21. Rettew JA, McCall SH, Marriott I. GPR30/GPER-1 mediates rapid decreases in TLR4 expression on murine macrophages. Mol Cell Endocrinol, 2010, 328(1-2): 87-92.
22. Brunsing RL, Owens KS, Prossnitz ER. The G protein-coupled estrogen receptor (GPER) agonist G-1 expands the regulatory T-cell population under TH17-polarizing conditions. J Immunother, 2013, 36(3): 190-196.
23. Kim MJ, Kim TH, Lee HH. G-protein coupled estrogen receptor (GPER/GPR30) and women’s health. J Menopausal Med, 2015, 21(2): 79-81.
24. Pupo M, Pisano A, Abonante S, et al. GPER activates notch signaling in breast cancer cells and cancer-associated fibroblasts (CAFs). Int J Biochem Cell Biol, 2014, 46: 56-67.
25. Li Y, Chen Y, Zhu ZX, et al. 4-Hydroxytamoxifen-stimulated processing of cyclinE is mediated via G protein-coupled receptor 30 (GPR30) and accompanied by enhanced migration in MCF-7 breast cancer cells. Toxicology, 2013, 309: 61-65.
26. Girgert R, Emons G, Gründker C. 17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib. Oncol Rep, 2017, 37(2): 1212-1218.
27. Yan Y, Jiang X, Zhao Y, et al. Role of GPER on proliferation, migration and invasion in ligand-independent manner in human ovarian cancer cell line SKOV3. Cell Biochem Funct, 2015, 33(8): 552-559.
28. Feldman RD, Ding Q, Hussain Y, et al. Aldosterone mediates metastatic spread of renal cancer via the G protein-coupled estrogen receptor (GPER). FASEB J, 2016, 30(6): 2086-2096.
29. Rudelius M, Rauert-Wunderlich H, Hartmann E, et al. The G protein-coupled estrogen receptor 1 (GPER-1) contributes to the proliferation and survival of mantle cell lymphoma cells. Haematologica, 2015, 100(11): e458-e461.
30. Zhang Q, Wu YZ, Zhang YM, et al. Activation of G-protein coupled estrogen receptor inhibits the proliferation of cervical cancer cells via sustained activation of ERK1/2. Cell Biochem Funct, 2015, 33(3): 134-142.
31. Mori T, Ito F, Matsushima H, et al. G protein-coupled estrogen receptor 1 agonist G-1 induces cell cycle arrest in the mitotic phase, leading to apoptosis in endometriosis. Fertil Steril, 2015, 103(5): 1228-1235.
32. Huff MO, Todd SL, Smith AL, et al. Arsenite and cadmium activate MAPK/ERK via membrane estrogen receptors and g-protein coupled estrogen receptor signaling in human lung adenocarcinoma cells. Toxicol Sci, 2016, 152(1): 62-71.
33. Liu CY, Liao YD, Fan S, et al. G protein-coupled estrogen receptor (GPER) mediates NSCLC progression induced by 17β-estradiol (E ₂) and selective agonist G1. Med Oncol, 2015, 32(4): 104.
34. Zhang KS, Chen HQ, Chen YS, et al. Bisphenol A stimulates human lung cancer cell migration via upregulation of matrix metalloproteinases by GPER/EGFR/ERK1/2 signal pathway. Biomed Pharmacother, 2014, 68(8): 1037-1043.
35. Zhu G, Huang Y, Wu C, et al. Activation of G-protein-coupled estrogen receptor inhibits the migration of human nonsmall cell lung cancer cells via IKK-β/NF-κB signals. DNA Cell Biol, 2016, 35(8): 434-442.
36. Gui Y, Shi Z, Wang Z, et al. The GPER agonist G-1 induces mitotic arrest and apoptosis in human vascular smooth muscle cells independent of GPER. J Cell Physiol, 2015, 230(4): 885-895.
37. The ENFUMOSA Study Group. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. European Network for Understanding Mechanisms of Severe Asthma. Eur Respir, 2003, 22(3): 470-477.
38. Cai Y, Zhou J, Webb DC. Estrogen stimulates Th2 cytokine production and regulates the compartmentalisation of eosinophils during allergen challenge in a mouse model of asthma. Int Arch Allergy Immunol, 2012, 158(3): 252-260.
39. Tamaki M, Konno Y, Kobayashi Y, et al. Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils. Immunol Lett, 2014, 160(1): 72-78.
40. Itoga M, Konno Y, Moritoki Y, et al. G-protein-coupled estrogen receptor agonist suppresses airway inflammation in a mouse model of asthma through IL-10. PLoS One, 2015, 10(3): e0123210.
41. Hao Y, Chow AW, Yip WC, et al. G protein-coupled estrogen receptor inhibits the P2Y receptor-mediated Ca²⁺ signaling pathway in human airway epithelia. Pflugers Arch, 2016, 468(8): 1489-1503.
42. Austin ED, Lahm T, West J, et al. Gender, sex hormones and pulmonary hypertension. Pulm Circ, 2013, 3(2): 294-314.
43. Huang S, Chen P, Shui X, et al. Baicalin attenuates transforming growth factor-β1-induced human pulmonary artery smooth muscle cell proliferation and phenotypic switch by inhibiting hypoxia inducible factor-1α and aryl hydrocarbon receptor expression. J Pharm Pharmacol, 2014, 66(10): 1469-1477.
44. Fernandez RA, Wan J, Song S, et al. Upregulated expression of STIM2, TRPC6, and Orai2 contributes to the transition of pulmonary arterial smooth muscle cells from a contractile to proliferative phenotype. Am J Physiol Cell Physiol, 2015 308(8): C581-C593.
45. Coll-Bonfill N, Musri MM, Ivo V, et al. Transdifferentiation of endothelial cells to smooth muscle cells play an important role in vascular remodelling. Am J Stem Cells, 2015, 4(1): 13-21.
46. Lindsey SH, da Silva AS, Silva MS, et al. Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation. Am J Physiol Endocrinol Metab, 2013, 305: E113-E118.
47. Koganti S, Snyder R, Gumaste U, et al. 2-methoxyestradiol binding of GPR30 down-regulates angiotensin AT1 receptor. Eur J Pharmacol, 2014, 723: 131-140.
48. Han G, White RE. G-protein-coupled estrogen receptor as a new therapeutic target for treating coronary artery disease. World J Cardiol, 2014, 6(6): 367-375.
49. Zhao Z, Wang H, Jessup JA, et al. Role of estrogen in diastolic dysfunction. Am J Physiol Heart Circ Physiol, 2014, 306(5): H628-H640.
50. Reslan OM, Yin Z, do Nascimento GR, et al. Subtype-specific estrogen receptor-mediated vasodilator activity in the cephalic, thoracic, and abdominal vasculature of female rat. J Cardiovasc Pharmacol, 2013, 62(1): 26-40.
51. Alencar AK, Montes GC, Montagnoli T, et al. Activation of GPER ameliorates experimental pulmonary hypertension in male rats. Eur J Pharm Sci, 2017, 97: 208-217.

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G 蛋白偶联雌激素受体信号通路与肺脏疾病

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