抑癌基因 PTEN 与特发性肺间质纤维化_Chinese Journal of Respiratory and Critical Care Medicine

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刘春雨 ,  高占成

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高占成, Email: gaozhancheng5446@163.com

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DOI：

10.7507/1671-6205.201708021

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Citation： 刘春雨, 高占成. 抑癌基因 PTEN 与特发性肺间质纤维化. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(2): 200-205. doi: 10.7507/1671-6205.201708021 Copy

1.	Fujimoto H, Kobayashi T, Azuma A. Idiopathic Pulmonary Fibrosis: Treatment and Prognosis. Clin Med Insights Circ Respir Pulm Med, 2015, 9(Suppl 1): 179-185.
2.	Raghu G, Rochwerg B, Zhang Y, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med, 2015, 192(2): e3-19.
3.	Brownell R, Kaminski N, Woodruff PG, et al. Precision Medicine: The New Frontier in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med, 2016, 193(11): 1213-1218.
4.	Martinez FJ, Chisholm A, Collard HR, et al. The diagnosis of idiopathic pulmonary fibrosis: current and future approaches. Lancet Respir Med, 2017, 5(1): 61-71.
5.	蔡后荣. 2011 年特发性肺纤维化诊断和治疗循证新指南解读. 中国呼吸与危重监护杂志, 2011, 10: 313-316.
6.	曹孟淑, 蔡后荣, 代华平. 2015ATS/ERS/JRS/ALAT 官方的临床实践指南: 特发性肺纤维化的治疗(执行摘要)——对 2011 年临床指南的更新. 中国呼吸与危重监护杂志, 2016, 15: 189-197.
7.	Gribbin J, Hubbard RB, Le JI, et al. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax, 2006, 61(11): 980-985.
8.	Awadalla NJ, Hegazy A, Elmetwally RA, et al. Occupational and environmental risk factors for idiopathic pulmonary fibrosis in Egypt: a multicenter case-control study. Int J Occup Environ Med, 2012, 3(3): 107-116.
9.	Martínez P, Blasco MA. Telomere-driven diseases and telomere-targeting therapies. J Cell Biol, 2017, 216(4): 875-887.
10.	Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308): 1943-1947.
11.	Liaw D, Marsh DJ, Li J, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet, 1997, 16(1): 64-67.
12.	Steck PA, Pershouse MA, Jasser SA, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 1997, 15(4): 356-362.
13.	Lee JO, Yang H, Georgescu MM, et al. Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell, 1999, 99(3): 323-334.
14.	Hopkins BD, Fine B, Steinbach N, et al. A secreted PTEN phosphatase that enters cells to alter signaling and survival. Science, 2013, 341(6144): 399-402.
15.	Liang H, He S, Yang J, et al. PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism. Cell Metab, 2014, 19(5): 836-848.
16.	Song MS, Salmena L, Carracedo A, et al. The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature, 2008, 455(7214): 813-817.
17.	Van Themsche C, Leblanc V, Parent S, et al. X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization. J Biol Chem, 2009, 284(31): 20462-20466.
18.	Howitt J, Low LH, Putz U, et al. Ndfip1 represses cell proliferation by controlling Pten localization and signaling specificity. J Mol Cell Biol, 2015, 7(2): 119-131.
19.	Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci, 2001, 114(Pt 13): 2375-2382.
20.	Shen WH, Balajee AS, Wang J, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell, 2007, 128(1): 157-170.
21.	Chen ZH, Zhu M, Yang J, et al. PTEN interacts with histone H1 and controls chromatin condensation. Cell Rep, 2014, 8(6): 2003-2014.
22.	Sun Z, Huang C, He J, et al. PTEN C-terminal deletion causes genomic instability and tumor development. Cell Rep, 2014, 6(5): 844-854.
23.	Planchon SM, Waite KA, Eng C. The nuclear affairs of PTEN. J Cell Sci, 2008, 121(Pt 3): 249-253.
24.	Song MS, Carracedo A, Salmena L, et al. Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell, 2011, 144(2): 187-199.
25.	Jerde TJ. Phosphatase and Tensin Homologue: Novel Regulation by Developmental Signaling. J Signal Transduct, 2015, 2015: 1-13.
26.	Fingerlin TE, Murphy E, Zhang W, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet, 2013, 45(6): 613-620.
27.	Molyneaux PL, Maher TM. The role of infection in the pathogenesis of idiopathic pulmonary fibrosis. Eur Respir Rev, 2013, 22(129): 376-381.
28.	Milioli G, Bosi M, Poletti V, et al. Sleep and respiratory sleep disorders in idiopathic pulmonary fibrosis. Sleep Med Rev, 2016, 26: 57-63.
29.	Ghebre YT, Raghu G. Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs. Am J Respir Crit Care Med, 2016, 193(12): 1345-1352.
30.	Chilosi M, Carloni A, Rossi A, et al. Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema. Transl Res, 2013, 162(3): 156-1573.
31.	Plataki M, Koutsopoulos AV, Darivianaki K, et al. Expression of apoptotic and antiapoptotic markers in epithelial cells in idiopathic pulmonary fibrosis. Chest, 2005, 127(1): 266-274.
32.	King TE, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet, 2011, 378(9807): 1949-1961.
33.	Tsujino K, Takeda Y, Arai T, et al. Tetraspanin CD151 protects against pulmonary fibrosis by maintaining epithelial integrity. Am J Respir Crit Care Med, 2012, 186(2): 170-180.
34.	Zhang X, Zhang Y, Tao B, et al. Loss of Shp2 in alveoli epithelia induces deregulated surfactant homeostasis, resulting in spontaneous pulmonary fibrosis. FASEB J, 2012, 26(6): 2338-2350.
35.	Shannon JM, Hyatt BA. Epithelial-mesenchymal interactions in the developing lung. Annu Rev Physiol, 2004, 66: 625-645.
36.	Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol, 2005, 17(5): 548-558.
37.	Chambers RC, Mercer PF. Mechanisms of alveolar epithelial injury, repair, and fibrosis. Ann Am Thorac Soc, 2015, 12 Suppl 1: S16-S20.
38.	Munger JS, Huang X, Kawakatsu H, et al. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell, 1999, 96(3): 319-328.
39.	Fontana L, Chen Y, Prijatelj P, et al. Fibronectin is required for integrin alphavbeta6-mediated activation of latent TGF-beta complexes containing LTBP-1. FASEB J, 2005, 19(13): 1798-1808.
40.	Kim Y, Kugler MC, Wei Y, et al. Integrin alpha3beta1-dependent beta-catenin phosphorylation links epithelial Smad signaling to cell contacts. J Cell Biol, 2009, 184(2): 309-322.
41.	Xu MY, Porte J, Knox AJ, et al. Lysophosphatidic acid induces alphavbeta6 integrin-mediated TGF-beta activation via the LPA2 receptor and the small G protein G alpha(q). Am J Pathol, 2009, 174(4): 1264-1279.
42.	Königshoff M, Balsara N, Pfaff EM, et al. Functional Wnt signaling is increased in idiopathic pulmonary fibrosis. PLoS One, 2008, 3(5): e2142.
43.	Bolaños AL, Milla CM, Lira JC, et al. Role of Sonic Hedgehog in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol, 2012, 303(11): L978-L990.
44.	Hu B, Liu J, Wu Z, et al. Reemergence of hedgehog mediates epithelial-mesenchymal crosstalk in pulmonary fibrosis. Am J Respir Cell Mol Biol, 2015, 52(4): 418-428.
45.	Phillips RJ, Burdick MD, Hong K, et al. Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest, 2004, 114(3): 438-446.
46.	Hinz B, Phan SH, Thannickal VJ, et al. Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol, 2012, 180(4): 1340-1355.
47.	Milella M, Falcone I, Conciatori F, et al. PTEN: Multiple Functions in Human Malignant Tumors. Front Oncol, 2015, 5: 24.
48.	White ES, Atrasz RG, Hu B, et al. Negative regulation of myofibroblast differentiation by PTEN (Phosphatase and Tensin Homolog Deleted on chromosome 10). Am J Respir Crit Care Med, 2006, 173(1): 112-121.
49.	Xia H, Khalil W, Kahm J, et al. Pathologic caveolin-1 regulation of PTEN in idiopathic pulmonary fibrosis. Am J Pathol, 2010, 176(6): 2626-2637.
50.	Geng J, Huang X, Li Y, et al. Down-regulation of USP13 mediates phenotype transformation of fibroblasts in idiopathic pulmonary fibrosis. Respir Res, 2015, 16: 124.
51.	Miyoshi K, Yanagi S, Kawahara K, et al. Epithelial Pten controls acute lung injury and fibrosis by regulating alveolar epithelial cell integrity. Am J Respir Crit Care Med, 2013, 187(3): 262-275.
52.	Geng J, Huang X, Li Y, et al. Phosphatase and tensin homolog deleted on chromosome 10 contributes to phenotype transformation of fibroblasts in idiopathic pulmonary fibrosis via multiple pathways. Exp Biol Med (Maywood), 2016, 241(2): 157-165.
53.	Oehrle B, Burgstaller G, Irmler M, et al. Validated prediction of pro-invasive growth factors using a transcriptome-wide invasion signature derived from a complex 3D invasion assay. Sci Rep, 2015, 5: 12673.
54.	Nho RS, Xia H, Diebold D, et al. PTEN regulates fibroblast elimination during collagen matrix contraction. J Biol Chem, 2006, 281(44): 33291-33301.
55.	Xia H, Diebold D, Nho R, et al. Pathological integrin signaling enhances proliferation of primary lung fibroblasts from patients with idiopathic pulmonary fibrosis. J Exp Med, 2008, 205(7): 1659-1672.
56.	Nho RS, Hergert P. IPF fibroblasts are desensitized to type I collagen matrix-induced cell death by suppressing low autophagy via aberrant Akt/mTOR kinases. PLoS One, 2014, 9(4): e94616.
57.	Nho RS, Hergert P, Kahm J, et al. Pathological alteration of FoxO3a activity promotes idiopathic pulmonary fibrosis fibroblast proliferation on type i collagen matrix. Am J Pathol, 2011, 179(5): 2420-2430.
58.	Nho RS, Peterson M, Hergert P, et al. FoxO3a (Forkhead Box O3a) deficiency protects Idiopathic Pulmonary Fibrosis (IPF) fibroblasts from type I polymerized collagen matrix-induced apoptosis via caveolin-1 (cav-1) and Fas. PLoS One, 2013, 8(4): e61017.
59.	Im J, Hergert P, Nho RS. Reduced FoxO3a expression causes low autophagy in idiopathic pulmonary fibrosis fibroblasts on collagen matrices. Am J Physiol Lung Cell Mol Physiol, 2015, 309(6): L552-L561.
60.	Huang SK, Fisher AS, Scruggs AM, et al. Hypermethylation of PTGER2 confers prostaglandin E2 resistance in fibrotic fibroblasts from humans and mice. Am J Pathol, 2010, 177(5): 2245-2255.
61.	Kral JB, Kuttke M, Schrottmaier WC, et al. Sustained PI3K Activation exacerbates BLM-induced Lung Fibrosis via activation of pro-inflammatory and pro-fibrotic pathways. Sci Rep, 2016, 6: 23034.
62.	Kulkarni YM, Dutta S, Iyer AK, et al. A proteomics approach to identifying key protein targets involved in VEGF inhibitor mediated attenuation of bleomycin-induced pulmonary fibrosis. Proteomics, 2016, 16(1): 33-46.

1. Fujimoto H, Kobayashi T, Azuma A. Idiopathic Pulmonary Fibrosis: Treatment and Prognosis. Clin Med Insights Circ Respir Pulm Med, 2015, 9(Suppl 1): 179-185.
2. Raghu G, Rochwerg B, Zhang Y, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med, 2015, 192(2): e3-19.
3. Brownell R, Kaminski N, Woodruff PG, et al. Precision Medicine: The New Frontier in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med, 2016, 193(11): 1213-1218.
4. Martinez FJ, Chisholm A, Collard HR, et al. The diagnosis of idiopathic pulmonary fibrosis: current and future approaches. Lancet Respir Med, 2017, 5(1): 61-71.
5. 蔡后荣. 2011 年特发性肺纤维化诊断和治疗循证新指南解读. 中国呼吸与危重监护杂志, 2011, 10: 313-316.
6. 曹孟淑, 蔡后荣, 代华平. 2015ATS/ERS/JRS/ALAT 官方的临床实践指南: 特发性肺纤维化的治疗(执行摘要)——对 2011 年临床指南的更新. 中国呼吸与危重监护杂志, 2016, 15: 189-197.
7. Gribbin J, Hubbard RB, Le JI, et al. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax, 2006, 61(11): 980-985.
8. Awadalla NJ, Hegazy A, Elmetwally RA, et al. Occupational and environmental risk factors for idiopathic pulmonary fibrosis in Egypt: a multicenter case-control study. Int J Occup Environ Med, 2012, 3(3): 107-116.
9. Martínez P, Blasco MA. Telomere-driven diseases and telomere-targeting therapies. J Cell Biol, 2017, 216(4): 875-887.
10. Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308): 1943-1947.
11. Liaw D, Marsh DJ, Li J, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet, 1997, 16(1): 64-67.
12. Steck PA, Pershouse MA, Jasser SA, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 1997, 15(4): 356-362.
13. Lee JO, Yang H, Georgescu MM, et al. Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell, 1999, 99(3): 323-334.
14. Hopkins BD, Fine B, Steinbach N, et al. A secreted PTEN phosphatase that enters cells to alter signaling and survival. Science, 2013, 341(6144): 399-402.
15. Liang H, He S, Yang J, et al. PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism. Cell Metab, 2014, 19(5): 836-848.
16. Song MS, Salmena L, Carracedo A, et al. The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature, 2008, 455(7214): 813-817.
17. Van Themsche C, Leblanc V, Parent S, et al. X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization. J Biol Chem, 2009, 284(31): 20462-20466.
18. Howitt J, Low LH, Putz U, et al. Ndfip1 represses cell proliferation by controlling Pten localization and signaling specificity. J Mol Cell Biol, 2015, 7(2): 119-131.
19. Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci, 2001, 114(Pt 13): 2375-2382.
20. Shen WH, Balajee AS, Wang J, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell, 2007, 128(1): 157-170.
21. Chen ZH, Zhu M, Yang J, et al. PTEN interacts with histone H1 and controls chromatin condensation. Cell Rep, 2014, 8(6): 2003-2014.
22. Sun Z, Huang C, He J, et al. PTEN C-terminal deletion causes genomic instability and tumor development. Cell Rep, 2014, 6(5): 844-854.
23. Planchon SM, Waite KA, Eng C. The nuclear affairs of PTEN. J Cell Sci, 2008, 121(Pt 3): 249-253.
24. Song MS, Carracedo A, Salmena L, et al. Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell, 2011, 144(2): 187-199.
25. Jerde TJ. Phosphatase and Tensin Homologue: Novel Regulation by Developmental Signaling. J Signal Transduct, 2015, 2015: 1-13.
26. Fingerlin TE, Murphy E, Zhang W, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet, 2013, 45(6): 613-620.
27. Molyneaux PL, Maher TM. The role of infection in the pathogenesis of idiopathic pulmonary fibrosis. Eur Respir Rev, 2013, 22(129): 376-381.
28. Milioli G, Bosi M, Poletti V, et al. Sleep and respiratory sleep disorders in idiopathic pulmonary fibrosis. Sleep Med Rev, 2016, 26: 57-63.
29. Ghebre YT, Raghu G. Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs. Am J Respir Crit Care Med, 2016, 193(12): 1345-1352.
30. Chilosi M, Carloni A, Rossi A, et al. Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema. Transl Res, 2013, 162(3): 156-1573.
31. Plataki M, Koutsopoulos AV, Darivianaki K, et al. Expression of apoptotic and antiapoptotic markers in epithelial cells in idiopathic pulmonary fibrosis. Chest, 2005, 127(1): 266-274.
32. King TE, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet, 2011, 378(9807): 1949-1961.
33. Tsujino K, Takeda Y, Arai T, et al. Tetraspanin CD151 protects against pulmonary fibrosis by maintaining epithelial integrity. Am J Respir Crit Care Med, 2012, 186(2): 170-180.
34. Zhang X, Zhang Y, Tao B, et al. Loss of Shp2 in alveoli epithelia induces deregulated surfactant homeostasis, resulting in spontaneous pulmonary fibrosis. FASEB J, 2012, 26(6): 2338-2350.
35. Shannon JM, Hyatt BA. Epithelial-mesenchymal interactions in the developing lung. Annu Rev Physiol, 2004, 66: 625-645.
36. Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol, 2005, 17(5): 548-558.
37. Chambers RC, Mercer PF. Mechanisms of alveolar epithelial injury, repair, and fibrosis. Ann Am Thorac Soc, 2015, 12 Suppl 1: S16-S20.
38. Munger JS, Huang X, Kawakatsu H, et al. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell, 1999, 96(3): 319-328.
39. Fontana L, Chen Y, Prijatelj P, et al. Fibronectin is required for integrin alphavbeta6-mediated activation of latent TGF-beta complexes containing LTBP-1. FASEB J, 2005, 19(13): 1798-1808.
40. Kim Y, Kugler MC, Wei Y, et al. Integrin alpha3beta1-dependent beta-catenin phosphorylation links epithelial Smad signaling to cell contacts. J Cell Biol, 2009, 184(2): 309-322.
41. Xu MY, Porte J, Knox AJ, et al. Lysophosphatidic acid induces alphavbeta6 integrin-mediated TGF-beta activation via the LPA2 receptor and the small G protein G alpha(q). Am J Pathol, 2009, 174(4): 1264-1279.
42. Königshoff M, Balsara N, Pfaff EM, et al. Functional Wnt signaling is increased in idiopathic pulmonary fibrosis. PLoS One, 2008, 3(5): e2142.
43. Bolaños AL, Milla CM, Lira JC, et al. Role of Sonic Hedgehog in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol, 2012, 303(11): L978-L990.
44. Hu B, Liu J, Wu Z, et al. Reemergence of hedgehog mediates epithelial-mesenchymal crosstalk in pulmonary fibrosis. Am J Respir Cell Mol Biol, 2015, 52(4): 418-428.
45. Phillips RJ, Burdick MD, Hong K, et al. Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest, 2004, 114(3): 438-446.
46. Hinz B, Phan SH, Thannickal VJ, et al. Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol, 2012, 180(4): 1340-1355.
47. Milella M, Falcone I, Conciatori F, et al. PTEN: Multiple Functions in Human Malignant Tumors. Front Oncol, 2015, 5: 24.
48. White ES, Atrasz RG, Hu B, et al. Negative regulation of myofibroblast differentiation by PTEN (Phosphatase and Tensin Homolog Deleted on chromosome 10). Am J Respir Crit Care Med, 2006, 173(1): 112-121.
49. Xia H, Khalil W, Kahm J, et al. Pathologic caveolin-1 regulation of PTEN in idiopathic pulmonary fibrosis. Am J Pathol, 2010, 176(6): 2626-2637.
50. Geng J, Huang X, Li Y, et al. Down-regulation of USP13 mediates phenotype transformation of fibroblasts in idiopathic pulmonary fibrosis. Respir Res, 2015, 16: 124.
51. Miyoshi K, Yanagi S, Kawahara K, et al. Epithelial Pten controls acute lung injury and fibrosis by regulating alveolar epithelial cell integrity. Am J Respir Crit Care Med, 2013, 187(3): 262-275.
52. Geng J, Huang X, Li Y, et al. Phosphatase and tensin homolog deleted on chromosome 10 contributes to phenotype transformation of fibroblasts in idiopathic pulmonary fibrosis via multiple pathways. Exp Biol Med (Maywood), 2016, 241(2): 157-165.
53. Oehrle B, Burgstaller G, Irmler M, et al. Validated prediction of pro-invasive growth factors using a transcriptome-wide invasion signature derived from a complex 3D invasion assay. Sci Rep, 2015, 5: 12673.
54. Nho RS, Xia H, Diebold D, et al. PTEN regulates fibroblast elimination during collagen matrix contraction. J Biol Chem, 2006, 281(44): 33291-33301.
55. Xia H, Diebold D, Nho R, et al. Pathological integrin signaling enhances proliferation of primary lung fibroblasts from patients with idiopathic pulmonary fibrosis. J Exp Med, 2008, 205(7): 1659-1672.
56. Nho RS, Hergert P. IPF fibroblasts are desensitized to type I collagen matrix-induced cell death by suppressing low autophagy via aberrant Akt/mTOR kinases. PLoS One, 2014, 9(4): e94616.
57. Nho RS, Hergert P, Kahm J, et al. Pathological alteration of FoxO3a activity promotes idiopathic pulmonary fibrosis fibroblast proliferation on type i collagen matrix. Am J Pathol, 2011, 179(5): 2420-2430.
58. Nho RS, Peterson M, Hergert P, et al. FoxO3a (Forkhead Box O3a) deficiency protects Idiopathic Pulmonary Fibrosis (IPF) fibroblasts from type I polymerized collagen matrix-induced apoptosis via caveolin-1 (cav-1) and Fas. PLoS One, 2013, 8(4): e61017.
59. Im J, Hergert P, Nho RS. Reduced FoxO3a expression causes low autophagy in idiopathic pulmonary fibrosis fibroblasts on collagen matrices. Am J Physiol Lung Cell Mol Physiol, 2015, 309(6): L552-L561.
60. Huang SK, Fisher AS, Scruggs AM, et al. Hypermethylation of PTGER2 confers prostaglandin E2 resistance in fibrotic fibroblasts from humans and mice. Am J Pathol, 2010, 177(5): 2245-2255.
61. Kral JB, Kuttke M, Schrottmaier WC, et al. Sustained PI3K Activation exacerbates BLM-induced Lung Fibrosis via activation of pro-inflammatory and pro-fibrotic pathways. Sci Rep, 2016, 6: 23034.
62. Kulkarni YM, Dutta S, Iyer AK, et al. A proteomics approach to identifying key protein targets involved in VEGF inhibitor mediated attenuation of bleomycin-induced pulmonary fibrosis. Proteomics, 2016, 16(1): 33-46.

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抑癌基因 PTEN 与特发性肺间质纤维化

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