Notch信号通路对支气管发育影响的研究进展_West China Medical Journal

Authors：

 杨立勋 , 刘敏 ,  徐畅

四川大学华西医院小儿外科（成都 610041）;

Corresponding author：

徐畅, Email: xcxcxc52229081@163.com

Keywords：

Notch信号通路; 支气管发育; 支气管肺发育不良

DOI：

10.7507/1002-0179.201600102

Video：

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Abstract Full text Figures/Tables Video References Cited by

支气管肺发育不良已成为新生儿最常见的呼吸系统疾病，严重影响新生儿存活率。Notch信号转导通路是一条在进化上高度保守的信号途径，其生物学效应广泛，近年来越来越多的证据表明Notch信号通路对支气管的正常发育有重要调节作用。通过对Notch信号通路对支气管发育影响的进展进行综述，了解Notch信号通路对支气管发育的作用机制，会为支气管肺发育不良的防治提供依据，或许会成为治疗支气管肺发育不良新的切入点。

Citation： 杨立勋, 刘敏, 徐畅. Notch信号通路对支气管发育影响的研究进展. West China Medical Journal, 2016, 31(2): 379-383. doi: 10.7507/1002-0179.201600102 Copy

1.	Somaschini M, Castiglioni E, Volonteri C, et al. Genetic predisposing factors to bronchopulmonary dysplasia:preliminary data from a multicentre study[J]. J Matern Fetal Neonatal Med, 2012, 25(Suppl 4):127-130.
2.	Kirpalani H, Millar D, Lemyre B, et al. A trial comparing noninvasive ventilation strategies in preterm infants[J]. N Engl J Med, 2013, 369(7):611-620.
3.	Xu C, Liu W, Wang Y, et al. Prenatal tetrandrine treatment can reverse the abnormal conditions in the lung of newborn with congenital diaphragmatic hernia[J]. Med Hypotheses, 2009, 72(5):570-573.
4.	Chang E. Preterm birth and the role of neuroprotection[Z], 2015:g6661.
5.	Ronan S, Liberatos P, Weingarten S, et al. Development of home educational materials for families of preterm infants[J]. Neonatal Netw, 2015, 34(2):102-112.
6.	Xu KL, Moghal N, Egan SE. Notch signaling in lung development and disease[J]. Adv Exp Med Biol, 2012(727):89-98.
7.	Wang H, Tian Y, Wang J, et al. Inflammatory cytokines induce NOTCH signaling in nucleus pulposus cells:implications in intervertebral disc degeneration[J]. J Biol Chem, 2013, 288(23):16761-16774.
8.	Tolcher AW, Messersmith WA, Mikulski SM, et al. Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors[J]. J Clin Oncol, 2012, 30(19):2348-2353.
9.	Fuwa TJ, Hori K, Sasamura T, et al. The first deltex null mutant indicates tissue-specific deltex-dependent Notch signaling in Drosophila[J]. Mol Genet Genomics, 2006, 275(3):251-263.
10.	Hu H, Zhou L, Awadallah A, et al. Significance of notch1-signaling pathway in human pancreatic development and carcinogenesis[J]. Appl Immunohistochem Mol Morphol, 2013, 21(3):242-247.
11.	Afelik S, Jensen J. Notch signaling in the pancreas:patterning and cell fate specification[J]. Wiley Interdiscip Rev Dev Biol, 2013, 2(4):531-544.
12.	Yu B, Song B. Notch 1 signalling inhibits cardiomyocyte apoptosis in ischaemic postconditioning[J]. Heart Lung Circ, 2014, 23(2):152-158.
13.	Morell CM, Strazzabosco M. Notch signaling and new therapeutic options in liver disease[J]. J Hepatol, 2014, 60(4):885-890.
14.	Yao L, Cao Q, Wu C, et al. Notch signaling in the central nervous system with special reference to its expression in microglia[J]. CNS Neurol Disord Drug Targets, 2013, 12(6):807-814.
15.	Adam MG, Berger C, Feldner A, et al. Synaptojanin-2 binding protein stabilizes the Notch ligands DLL1 and DLL4 and inhibits sprouting angiogenesis[J]. Circ Res, 2013, 113(11):1206-1218.
16.	Tomlinson A, Mavromatakis YE, Struhl G. Three distinct roles for notch in Drosophila R7 photoreceptor specification[J]. PLoS Biol, 2011, 9(8):e1001132.
17.	Auderset F, Schuster S, Fasnacht N, et al. Notch signaling regulates follicular helper T cell differentiation[J]. J Immunol, 2013, 191(5):2344-2350.
18.	Suman S, Das TP, Damodaran C. Silencing NOTCH signaling causes growth arrest in both breast cancer stem cells and breast cancer cells[J]. Br J Cancer, 2013, 109(10):2587-2596.
19.	Kim JH, Thimmulappa RK, Kumar V, et al. NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation[J]. J Clin Invest, 2014, 124(2):730-741.
20.	Srivastava S, Ramdass B, Nagarajan S, et al. Notch1 regulates the functional contribution of RhoC to cervical carcinoma progression[J]. Br J Cancer, 2010, 102(1):196-205.
21.	Gorantla B, Bhoopathi P, Chetty C, et al. Notch signaling regulates tumor-induced angiogenesis in SPARC-overexpressed neuroblastoma[J]. Angiogenesis, 2013, 16(1):85-100.
22.	Xie M, He CS, Wei SH, et al. Notch-1 contributes to epidermal growth factor receptor tyrosine kinase inhibitor acquired resistance in non-small cell lung cancer in vitro and in vivo[J]. Eur J Cancer, 2013, 49(16):3559-3572.
23.	Du X, Zhao YP, Zhang TP, et al. Alteration of the intrinsic apoptosis pathway is involved in Notch-induced chemoresistance to gemcitabine in pancreatic cancer[J]. Arch Med Res, 2014, 45(1):15-20.
24.	Ito T, Udaka N, Yazawa T, et al. Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium[J]. Development, 2000, 127(18):3913-3921.
25.	Taichman DB, Loomes KM, Schachtner SK, et al. Notch1 and jagged1 expression by the developing pulmonary vasculature[J]. Dev Dyn, 2002, 225(2):166-175.
26.	Post LC, Ternet M, Hogan BL. Notch/delta expression in the developing mouse lung[J]. Mech Dev, 2000, 98(1/2):95-98.
27.	Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling:cell fate control and signal integration in development[J]. Science, 1999, 284(5415):770-776.
28.	Dang TP, Eichenberger S, Gonzalez A, et al. Constitutive activation of Notch3 inhibits terminal epithelial differentiation in lungs of transgenic mice[J]. Oncogene, 2003, 22(13):1988-1997.
29.	Ahmed Z, Bicknell R. Angiogenic signalling pathways[J]. Methods Mol Biol, 2009, 467(10):3-24.
30.	Sacilotto N, Monteiro R, Fritzsche M, et al. Analysis of Dll4 regulation reveals a combinatorial role for Sox and Notch in arterial development[J]. Proc Natl Acad Sci U S A, 2013, 110(29):11893-11898.
31.	Miniati D, Jelin EB, Ng J, et al. Constitutively active endothelial Notch4 causes lung arteriovenous shunts in mice[J]. Am J Physiol Lung Cell Mol Physiol, 2010, 298(2):L169-L177.
32.	Kong Y, Glickman J, Subramaniam M, et al. Functional diversity of notch family genes in fetal lung development[J]. Am J Physiol Lung Cell Mol Physiol, 2004, 286(5):L1075-L1083.
33.	Tsao PN, Chen F, Izvolsky KI, et al. Gamma-secretase activation of notch signaling regulates the balance of proximal and distal fates in progenitor cells of the developing lung[J]. J Biol Chem, 2008, 283(43):29532-29544.
34.	Yevtodiyenko A, Schmidt JV. Dlk1 expression marks developing endothelium and sites of branching morphogenesis in the mouse embryo and placenta[J]. Dev Dyn, 2006, 235(4):1115-1123.
35.	Morimoto M, Nishinakamura R, Saga Y, et al. Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells[J]. Development, 2012, 139(23):4365-4373.
36.	Konishi S, Gotoh S, Tateishi K, et al. Directed induction of functional multi-ciliated cells in proximal airway epithelial spheroids from human pluripotent stem cells[J]. Stem Cell Reports, 2016, 6(1):18-25.
37.	Morimoto M, Liu Z, Cheng HT, et al. Canonical notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of clara versus ciliated cell fate[J]. J Cell Sci, 2010, 123(Pt 2):213-224.
38.	Tsao PN, Vasconcelos M, Izvolsky KI, et al. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways[J]. Development, 2009, 136(13):2297-2307.
39.	Shan L, Aster JC, Sklar J, et al. Notch-1 regulates pulmonary neuroendocrine cell differentiation in cell lines and in transgenic mice[J]. Am J Physiol Lung Cell Mol Physiol, 2007, 292(2):L500-L509.
40.	Guseh JS, Bores SA, Stanger BZ, et al. Notch signaling promotes airway mucous metaplasia and inhibits alveolar development[J]. Development, 2009, 136(10):1751-1759.
41.	Xing Y, Li A, Borok Z, et al. NOTCH1 is required for regeneration of Clara cells during repair of airway injury[J]. Stem Cells, 2012, 30(5):946-955.
42.	Zhang S, Loch AJ, Radtke F, et al. Jagged1 is the major regulator of Notch-dependent cell fate in proximal airways[J]. Dev Dyn, 2013, 242(6):678-686.
43.	Boucherat O, Chakir J, Jeannotte L. The loss of Hoxa5 function promotes Notch-dependent goblet cell metaplasia in lung airways[J]. Biol Open, 2012, 1(7):677-691.
44.	Tsao PN, Wei SC, Wu MF, et al. Notch signaling prevents mucous metaplasia in mouse conducting airways during postnatal development[J]. Development, 2011, 138(16):3533-3543.

1. Somaschini M, Castiglioni E, Volonteri C, et al. Genetic predisposing factors to bronchopulmonary dysplasia:preliminary data from a multicentre study[J]. J Matern Fetal Neonatal Med, 2012, 25(Suppl 4):127-130.
2. Kirpalani H, Millar D, Lemyre B, et al. A trial comparing noninvasive ventilation strategies in preterm infants[J]. N Engl J Med, 2013, 369(7):611-620.
3. Xu C, Liu W, Wang Y, et al. Prenatal tetrandrine treatment can reverse the abnormal conditions in the lung of newborn with congenital diaphragmatic hernia[J]. Med Hypotheses, 2009, 72(5):570-573.
4. Chang E. Preterm birth and the role of neuroprotection[Z], 2015:g6661.
5. Ronan S, Liberatos P, Weingarten S, et al. Development of home educational materials for families of preterm infants[J]. Neonatal Netw, 2015, 34(2):102-112.
6. Xu KL, Moghal N, Egan SE. Notch signaling in lung development and disease[J]. Adv Exp Med Biol, 2012(727):89-98.
7. Wang H, Tian Y, Wang J, et al. Inflammatory cytokines induce NOTCH signaling in nucleus pulposus cells:implications in intervertebral disc degeneration[J]. J Biol Chem, 2013, 288(23):16761-16774.
8. Tolcher AW, Messersmith WA, Mikulski SM, et al. Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors[J]. J Clin Oncol, 2012, 30(19):2348-2353.
9. Fuwa TJ, Hori K, Sasamura T, et al. The first deltex null mutant indicates tissue-specific deltex-dependent Notch signaling in Drosophila[J]. Mol Genet Genomics, 2006, 275(3):251-263.
10. Hu H, Zhou L, Awadallah A, et al. Significance of notch1-signaling pathway in human pancreatic development and carcinogenesis[J]. Appl Immunohistochem Mol Morphol, 2013, 21(3):242-247.
11. Afelik S, Jensen J. Notch signaling in the pancreas:patterning and cell fate specification[J]. Wiley Interdiscip Rev Dev Biol, 2013, 2(4):531-544.
12. Yu B, Song B. Notch 1 signalling inhibits cardiomyocyte apoptosis in ischaemic postconditioning[J]. Heart Lung Circ, 2014, 23(2):152-158.
13. Morell CM, Strazzabosco M. Notch signaling and new therapeutic options in liver disease[J]. J Hepatol, 2014, 60(4):885-890.
14. Yao L, Cao Q, Wu C, et al. Notch signaling in the central nervous system with special reference to its expression in microglia[J]. CNS Neurol Disord Drug Targets, 2013, 12(6):807-814.
15. Adam MG, Berger C, Feldner A, et al. Synaptojanin-2 binding protein stabilizes the Notch ligands DLL1 and DLL4 and inhibits sprouting angiogenesis[J]. Circ Res, 2013, 113(11):1206-1218.
16. Tomlinson A, Mavromatakis YE, Struhl G. Three distinct roles for notch in Drosophila R7 photoreceptor specification[J]. PLoS Biol, 2011, 9(8):e1001132.
17. Auderset F, Schuster S, Fasnacht N, et al. Notch signaling regulates follicular helper T cell differentiation[J]. J Immunol, 2013, 191(5):2344-2350.
18. Suman S, Das TP, Damodaran C. Silencing NOTCH signaling causes growth arrest in both breast cancer stem cells and breast cancer cells[J]. Br J Cancer, 2013, 109(10):2587-2596.
19. Kim JH, Thimmulappa RK, Kumar V, et al. NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation[J]. J Clin Invest, 2014, 124(2):730-741.
20. Srivastava S, Ramdass B, Nagarajan S, et al. Notch1 regulates the functional contribution of RhoC to cervical carcinoma progression[J]. Br J Cancer, 2010, 102(1):196-205.
21. Gorantla B, Bhoopathi P, Chetty C, et al. Notch signaling regulates tumor-induced angiogenesis in SPARC-overexpressed neuroblastoma[J]. Angiogenesis, 2013, 16(1):85-100.
22. Xie M, He CS, Wei SH, et al. Notch-1 contributes to epidermal growth factor receptor tyrosine kinase inhibitor acquired resistance in non-small cell lung cancer in vitro and in vivo[J]. Eur J Cancer, 2013, 49(16):3559-3572.
23. Du X, Zhao YP, Zhang TP, et al. Alteration of the intrinsic apoptosis pathway is involved in Notch-induced chemoresistance to gemcitabine in pancreatic cancer[J]. Arch Med Res, 2014, 45(1):15-20.
24. Ito T, Udaka N, Yazawa T, et al. Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium[J]. Development, 2000, 127(18):3913-3921.
25. Taichman DB, Loomes KM, Schachtner SK, et al. Notch1 and jagged1 expression by the developing pulmonary vasculature[J]. Dev Dyn, 2002, 225(2):166-175.
26. Post LC, Ternet M, Hogan BL. Notch/delta expression in the developing mouse lung[J]. Mech Dev, 2000, 98(1/2):95-98.
27. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling:cell fate control and signal integration in development[J]. Science, 1999, 284(5415):770-776.
28. Dang TP, Eichenberger S, Gonzalez A, et al. Constitutive activation of Notch3 inhibits terminal epithelial differentiation in lungs of transgenic mice[J]. Oncogene, 2003, 22(13):1988-1997.
29. Ahmed Z, Bicknell R. Angiogenic signalling pathways[J]. Methods Mol Biol, 2009, 467(10):3-24.
30. Sacilotto N, Monteiro R, Fritzsche M, et al. Analysis of Dll4 regulation reveals a combinatorial role for Sox and Notch in arterial development[J]. Proc Natl Acad Sci U S A, 2013, 110(29):11893-11898.
31. Miniati D, Jelin EB, Ng J, et al. Constitutively active endothelial Notch4 causes lung arteriovenous shunts in mice[J]. Am J Physiol Lung Cell Mol Physiol, 2010, 298(2):L169-L177.
32. Kong Y, Glickman J, Subramaniam M, et al. Functional diversity of notch family genes in fetal lung development[J]. Am J Physiol Lung Cell Mol Physiol, 2004, 286(5):L1075-L1083.
33. Tsao PN, Chen F, Izvolsky KI, et al. Gamma-secretase activation of notch signaling regulates the balance of proximal and distal fates in progenitor cells of the developing lung[J]. J Biol Chem, 2008, 283(43):29532-29544.
34. Yevtodiyenko A, Schmidt JV. Dlk1 expression marks developing endothelium and sites of branching morphogenesis in the mouse embryo and placenta[J]. Dev Dyn, 2006, 235(4):1115-1123.
35. Morimoto M, Nishinakamura R, Saga Y, et al. Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells[J]. Development, 2012, 139(23):4365-4373.
36. Konishi S, Gotoh S, Tateishi K, et al. Directed induction of functional multi-ciliated cells in proximal airway epithelial spheroids from human pluripotent stem cells[J]. Stem Cell Reports, 2016, 6(1):18-25.
37. Morimoto M, Liu Z, Cheng HT, et al. Canonical notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of clara versus ciliated cell fate[J]. J Cell Sci, 2010, 123(Pt 2):213-224.
38. Tsao PN, Vasconcelos M, Izvolsky KI, et al. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways[J]. Development, 2009, 136(13):2297-2307.
39. Shan L, Aster JC, Sklar J, et al. Notch-1 regulates pulmonary neuroendocrine cell differentiation in cell lines and in transgenic mice[J]. Am J Physiol Lung Cell Mol Physiol, 2007, 292(2):L500-L509.
40. Guseh JS, Bores SA, Stanger BZ, et al. Notch signaling promotes airway mucous metaplasia and inhibits alveolar development[J]. Development, 2009, 136(10):1751-1759.
41. Xing Y, Li A, Borok Z, et al. NOTCH1 is required for regeneration of Clara cells during repair of airway injury[J]. Stem Cells, 2012, 30(5):946-955.
42. Zhang S, Loch AJ, Radtke F, et al. Jagged1 is the major regulator of Notch-dependent cell fate in proximal airways[J]. Dev Dyn, 2013, 242(6):678-686.
43. Boucherat O, Chakir J, Jeannotte L. The loss of Hoxa5 function promotes Notch-dependent goblet cell metaplasia in lung airways[J]. Biol Open, 2012, 1(7):677-691.
44. Tsao PN, Wei SC, Wu MF, et al. Notch signaling prevents mucous metaplasia in mouse conducting airways during postnatal development[J]. Development, 2011, 138(16):3533-3543.

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