Brain-derived neurotrophic factor in the airways.

Y S Prakash, Richard J Martin
Author Information
  1. Y S Prakash: Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55905, United States; Department of Physiology & Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, United States. Electronic address: prakash.ys@mayo.edu.
  2. Richard J Martin: Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, OH 44106, United States.

Abstract

In addition to their well-known roles in the nervous system, there is increasing recognition that neurotrophins such as brain derived neurotrophic factor (BDNF) as well as their receptors are expressed in peripheral tissues including the lung, and can thus potentially contribute to both normal physiology and pathophysiology of several diseases. The relevance of this family of growth factors lies in emerging clinical data indicating altered neurotrophin levels and function in a range of diseases including neonatal and adult asthma, sinusitis, influenza, and lung cancer. The current review focuses on 1) the importance of BDNF expression and signaling mechanisms in early airway and lung development, critical to both normal neonatal lung function and also its disruption in prematurity and insults such as inflammation and infection; 2) how BDNF, potentially derived from airway nerves modulate neurogenic control of airway tone, a key aspect of airway reflexes as well as dysfunctional responses to allergic inflammation; 3) the emerging idea that local BDNF production by resident airway cells such as epithelium and airway smooth muscle can contribute to normal airway structure and function, and to airway hyperreactivity and remodeling in diseases such as asthma. Furthermore, given its pleiotropic effects in the airway, BDNF may be a novel and appealing therapeutic target.

Keywords

References

  1. Pulm Pharmacol Ther. 2004;17(6):333-6 [PMID: 15564071]
  2. Curr Neurovasc Res. 2007 May;4(2):143-51 [PMID: 17504212]
  3. J Allergy Clin Immunol. 2012 Dec;130(6):1243-55 [PMID: 23026498]
  4. J Cell Mol Med. 2012 Apr;16(4):812-23 [PMID: 21651720]
  5. Am J Respir Cell Mol Biol. 2006 Aug;35(2):243-51 [PMID: 16574942]
  6. Am J Respir Cell Mol Biol. 2009 Nov;41(5):603-11 [PMID: 19213875]
  7. Prog Neurobiol. 2003 Apr;69(5):341-74 [PMID: 12787574]
  8. Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):163-5 [PMID: 10224367]
  9. Am J Physiol. 1991 Aug;261(2 Pt 1):L15-28 [PMID: 1872409]
  10. Br J Pharmacol. 2004 Feb;141(3):431-40 [PMID: 14718253]
  11. Clin Sci (Lond). 2006 Feb;110(2):167-73 [PMID: 16411893]
  12. Trends Neurosci. 1995 Jul;18(7):321-6 [PMID: 7571013]
  13. Prog Histochem Cytochem. 2004;39(3):131-82 [PMID: 15580762]
  14. Proc Am Thorac Soc. 2008 Sep 15;5(7):772-7 [PMID: 18757316]
  15. Trends Neurosci. 2012 Jul;35(7):431-40 [PMID: 22503537]
  16. Pharmacol Ther. 2013 Dec;140(3):290-305 [PMID: 23880290]
  17. Expert Opin Ther Targets. 2004 Oct;8(5):391-9 [PMID: 15469390]
  18. J Neurosci. 2007 Jun 13;27(24):6417-27 [PMID: 17567802]
  19. Eur J Pharmacol. 2004 Oct 1;500(1-3):453-65 [PMID: 15464052]
  20. J Appl Physiol (1985). 2002 Apr;92(4):1594-602 [PMID: 11896026]
  21. Biochim Biophys Acta. 2013 Dec;1833(12):2953-2960 [PMID: 23899746]
  22. Am J Respir Crit Care Med. 2005 Jul 15;172(2):233-7 [PMID: 15879412]
  23. Curr Med Chem. 2012;19(34):5768-73 [PMID: 22963560]
  24. Eur J Pharmacol. 2008 Oct 24;595(1-3):78-83 [PMID: 18700138]
  25. BMC Womens Health. 2011 Jun 03;11:24 [PMID: 21639909]
  26. Am J Respir Crit Care Med. 1998 Dec;158(6):2002-5 [PMID: 9847299]
  27. Pediatr Allergy Immunol. 2007 Jun;18(4):293-7 [PMID: 17584309]
  28. Biochem J. 2008 Aug 1;413(3):437-46 [PMID: 18452405]
  29. Am J Physiol Lung Cell Mol Physiol. 2012 May 1;302(9):L941-8 [PMID: 22345578]
  30. Respir Physiol Neurobiol. 2009 May 30;167(1):36-44 [PMID: 19135556]
  31. Int J Dev Neurosci. 2005 Oct;23(6):495-500 [PMID: 15978771]
  32. Neuropharmacology. 2014 Jan;76 Pt C:628-38 [PMID: 23752094]
  33. Adv Exp Med Biol. 2011;704:573-93 [PMID: 21290317]
  34. Adv Exp Med Biol. 2010;654:281-304 [PMID: 20217503]
  35. Biochemistry. 1995 Apr 4;34(13):4139-46 [PMID: 7703225]
  36. Am J Physiol Lung Cell Mol Physiol. 2005 Aug;289(2):L307-14 [PMID: 15821016]
  37. Transl Res. 2007 Nov;150(5):303-10 [PMID: 17964519]
  38. Endocr Rev. 2012 Feb;33(1):1-47 [PMID: 22240244]
  39. J Neurobiol. 1994 Nov;25(11):1386-403 [PMID: 7852993]
  40. Int J Biochem Cell Biol. 2008;40(9):1664-8 [PMID: 17681869]
  41. J Appl Physiol (1985). 2006 Sep;101(3):950-9 [PMID: 16645193]
  42. Rev Neurosci. 1997 Jan-Mar;8(1):13-27 [PMID: 9402642]
  43. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2687-92 [PMID: 20133810]
  44. J Neurosci. 2011 Oct 26;31(43):15407-15 [PMID: 22031887]
  45. Am J Respir Cell Mol Biol. 2011 Oct;45(4):768-80 [PMID: 21330466]
  46. Horm Behav. 1994 Dec;28(4):367-75 [PMID: 7729805]
  47. Clin Respir J. 2010 Jan;4(1):45-50 [PMID: 20298417]
  48. Am J Respir Cell Mol Biol. 1999 Apr;20(4):550-60 [PMID: 10100986]
  49. Am J Physiol Lung Cell Mol Physiol. 2013 Dec;305(12):L912-33 [PMID: 24142517]
  50. Exp Neurol. 2012 Dec;238(2):254-64 [PMID: 22982152]
  51. Can Respir J. 1998 Nov-Dec;5(6):491-8 [PMID: 10070177]
  52. Prog Brain Res. 2002;137:415-23 [PMID: 12440384]
  53. J Smooth Muscle Res. 2004 Oct;40(4-5):155-67 [PMID: 15655303]
  54. Physiology (Bethesda). 2005 Feb;20:70-8 [PMID: 15653842]
  55. Cerebellum. 2009 Sep;8(3):312-22 [PMID: 19238500]
  56. Ann N Y Acad Sci. 2010 Jun;1198:252-9 [PMID: 20536940]
  57. Curr Opin Pulm Med. 2005 Jan;11(1):1-6 [PMID: 15591881]
  58. J Biol Chem. 2001 Apr 20;276(16):12660-6 [PMID: 11152678]
  59. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10884-9 [PMID: 9724799]
  60. CNS Neurol Disord Drug Targets. 2008 Feb;7(1):46-62 [PMID: 18289031]
  61. Curr Opin Investig Drugs. 2010 May;11(5):535-42 [PMID: 20419599]
  62. Acta Paediatr. 2013 Jun;102(6):e247-50 [PMID: 23461616]
  63. Brain Res. 2005 May 24;1044(2):133-43 [PMID: 15885212]
  64. Prog Brain Res. 2004;146:325-33 [PMID: 14699972]
  65. Sarcoidosis Vasc Diffuse Lung Dis. 2005 Oct;22(3):186-94 [PMID: 16315781]
  66. J Allergy Clin Immunol. 2005 Sep;116(3):713-6 [PMID: 16159653]
  67. J Mol Cell Cardiol. 2010 Mar;48(3):440-4 [PMID: 19818795]
  68. Eur Respir J. 2000 Jun;15(6):1120-7 [PMID: 10885434]
  69. J Gen Physiol. 2006 Nov;128(5):509-22 [PMID: 17074976]
  70. Neuroscience. 2013 Jun 3;239:157-72 [PMID: 23069755]
  71. Cell Mol Life Sci. 2001 Jul;58(8):1061-6 [PMID: 11529499]
  72. Curr Neuropharmacol. 2009 Dec;7(4):276-85 [PMID: 20514207]
  73. Respir Res. 2010 Nov 08;11:156 [PMID: 21059230]
  74. J Neuroendocrinol. 2013 Nov;25(11):1163-72 [PMID: 24112361]
  75. Expert Rev Respir Med. 2010 Jun;4(3):395-411 [PMID: 20524922]
  76. BMC Neurosci. 2008 Dec 03;9 Suppl 2:S1 [PMID: 19090982]
  77. J Biol Chem. 1995 Aug 25;270(34):19669-72 [PMID: 7649974]
  78. Am J Respir Cell Mol Biol. 2010 Oct;43(4):452-7 [PMID: 19901346]
  79. Nat Rev Neurosci. 2005 Aug;6(8):603-14 [PMID: 16062169]
  80. J Cell Biol. 2004 Dec 20;167(6):1205-15 [PMID: 15596541]
  81. Pulm Pharmacol Ther. 2013 Feb;26(1):75-85 [PMID: 22800879]
  82. PLoS One. 2010 Jul 13;5(7):e11528 [PMID: 20644624]
  83. Trends Neurosci. 2005 Jan;28(1):5-11 [PMID: 15626491]
  84. Cytokine. 2011 Nov;56(2):218-23 [PMID: 21723144]
  85. Neuroscience. 2013 Jun 3;239:271-9 [PMID: 23380505]
  86. Pharmacol Ther. 2014 Jan;141(1):21-31 [PMID: 23954656]
  87. Allergy. 2009 Dec;64(12):1790-4 [PMID: 19895626]
  88. Int Arch Allergy Immunol. 2009;149(4):343-9 [PMID: 19295238]
  89. J Appl Physiol (1985). 2001 Jan;90(1):358-68 [PMID: 11133929]
  90. Diabetes Obes Metab. 2009 Nov;11 Suppl 4:180-8 [PMID: 19817800]
  91. World Neurosurg. 2015 Jan;83(1):120-31 [PMID: 23334003]
  92. Front Integr Neurosci. 2013 Jul 29;7:55 [PMID: 23908608]
  93. Pharmacol Ther. 2013 May;138(2):155-75 [PMID: 23348013]
  94. Am J Pathol. 2000 Oct;157(4):1247-58 [PMID: 11021829]
  95. Respir Physiol Neurobiol. 2010 Oct 31;173(3):213-22 [PMID: 20359553]
  96. J Neurochem. 2007 Mar;100(6):1515-30 [PMID: 17286628]
  97. Pharmacol Ther. 2008 Jan;117(1):52-76 [PMID: 17915332]
  98. Can J Physiol Pharmacol. 2005 Aug-Sep;83(8-9):725-32 [PMID: 16333374]
  99. J Neurosci Res. 2007 Feb 15;85(3):525-35 [PMID: 17149751]
  100. Brain Res. 2006 Jul 26;1101(1):36-42 [PMID: 16790237]
  101. Exp Neurol. 2012 May;235(1):70-7 [PMID: 21195072]
  102. Neuron. 2004 May 27;42(4):529-33 [PMID: 15157416]
  103. Curr Drug Targets. 2006 Aug;7(8):1005-10 [PMID: 16918328]
  104. Anat Sci Int. 2005 Mar;80(1):37-41 [PMID: 15794129]
  105. Cytokine Growth Factor Rev. 2012 Feb-Apr;23(1-2):15-24 [PMID: 22341689]
  106. Bioessays. 2004 Nov;26(11):1185-94 [PMID: 15499580]
  107. Pulm Pharmacol Ther. 2009 Oct;22(5):353-9 [PMID: 19121407]
  108. Am J Respir Cell Mol Biol. 1998 Feb;18(2):149-57 [PMID: 9476901]
  109. Curr Allergy Asthma Rep. 2009 Nov;9(6):484-90 [PMID: 19814922]
  110. Neuropsychiatr Dis Treat. 2009;5:433-49 [PMID: 19721723]
  111. Allergy Asthma Immunol Res. 2013 Nov;5(6):343-7 [PMID: 24179679]
  112. Stress. 2000 May;3(3):201-8 [PMID: 10938581]
  113. Int J Physiol Pathophysiol Pharmacol. 2012;4(4):188-200 [PMID: 23320132]
  114. Brain Res Brain Res Rev. 2002 Oct;40(1-3):292-300 [PMID: 12589927]
  115. Curr Opin Allergy Clin Immunol. 2010 Feb;10(1):82-6 [PMID: 19858714]
  116. Respir Res. 2006 Jan 29;7:18 [PMID: 16441896]
  117. Neuron. 2005 Apr 7;46(1):13-21 [PMID: 15820690]
  118. Ann N Y Acad Sci. 2003 May;992:241-9 [PMID: 12794063]
  119. Curr Alzheimer Res. 2009 Oct;6(5):419-23 [PMID: 19874265]
  120. Science. 2001 Nov 30;294(5548):1945-8 [PMID: 11729324]
  121. Am J Physiol Lung Cell Mol Physiol. 2011 Jul;301(1):L91-8 [PMID: 21515660]
  122. Curr Alzheimer Res. 2008 Feb;5(1):38-44 [PMID: 18288930]
  123. J Allergy Clin Immunol. 2006 Apr;117(4):787-94 [PMID: 16630935]
  124. Dev Dyn. 2001 May;221(1):48-60 [PMID: 11357193]
  125. World Allergy Organ J. 2010 Sep;3(9):235-8 [PMID: 23282800]
  126. Pediatr Pulmonol. 2009 Nov;44(11):1075-84 [PMID: 19824047]
  127. J Immunol. 2009 Apr 15;182(8):4705-12 [PMID: 19342646]
  128. Int Anesthesiol Clin. 2006 Spring;44(2):21-76 [PMID: 16849956]
  129. Respir Physiol Neurobiol. 2009 Jul 31;167(3):281-91 [PMID: 19523540]
  130. Gastroenterology. 2011 Jun;140(7):2107-15, 2115.e1-4 [PMID: 21354153]
  131. FEBS Lett. 2000 Mar 24;470(2):113-7 [PMID: 10734218]
  132. Pulm Pharmacol Ther. 2004;17(4):181-98 [PMID: 15219263]
  133. Endocrinology. 2004 May;145(5):2498-506 [PMID: 14764638]
  134. Eur Neuropsychopharmacol. 2005 May;15(3):319-29 [PMID: 15820422]
  135. Ann N Y Acad Sci. 1995 Sep 7;766:442-58 [PMID: 7486690]
  136. Organogenesis. 2013 Jul-Sep;9(3):194-8 [PMID: 23974176]
  137. Inflamm Allergy Drug Targets. 2009 Jul;8(3):176-81 [PMID: 19601877]
  138. Am J Physiol Lung Cell Mol Physiol. 2008 Aug;295(2):L348-55 [PMID: 18515408]
  139. Cytokine Growth Factor Rev. 2003 Dec;14(6):551-8 [PMID: 14563356]
  140. Am J Med. 1997 Sep 22;103(3A):19S-25S [PMID: 9344403]
  141. Curr Opin Allergy Clin Immunol. 2002 Feb;2(1):39-45 [PMID: 11964749]
  142. Nat Rev Neurosci. 2013 Jan;14(1):7-23 [PMID: 23254191]
  143. Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):1041-50 [PMID: 10195934]
  144. Neurosci Res. 2009 Sep;65(1):11-22 [PMID: 19523993]
  145. J Neurosci Res. 2007 Oct;85(13):2813-23 [PMID: 17387691]
  146. Clin Cancer Res. 2009 Oct 1;15(19):5962-7 [PMID: 19755385]
  147. Curr Opin Neurobiol. 2004 Oct;14(5):558-63 [PMID: 15464888]
  148. Clin Chim Acta. 2005 Feb;352(1-2):49-74 [PMID: 15653100]
  149. PLoS One. 2012;7(8):e44343 [PMID: 22952960]
  150. Am J Respir Cell Mol Biol. 2007 Mar;36(3):387-8 [PMID: 17297022]
  151. Nat Rev Drug Discov. 2013 Jul;12(7):507-25 [PMID: 23977697]
  152. Br J Pharmacol. 2008 Mar;153 Suppl 1:S310-24 [PMID: 18059328]
  153. Proc Am Thorac Soc. 2004;1(3):231-4 [PMID: 16113439]
  154. Sarcoidosis Vasc Diffuse Lung Dis. 2007 Mar;24(1):13-23 [PMID: 18069415]
  155. Clin Exp Allergy. 2000 Feb;30(2):178-86 [PMID: 10651769]
  156. J Appl Physiol (1985). 2006 Sep;101(3):971-85 [PMID: 16728519]
  157. Am J Respir Cell Mol Biol. 2004 Jan;30(1):12-9 [PMID: 12791675]
  158. Chest. 2013 Sep;144(3):1026-1032 [PMID: 24008953]
  159. Respir Physiol Neurobiol. 2003 Sep 16;137(2-3):209-22 [PMID: 14516727]
  160. Proc Am Thorac Soc. 2009 Dec;6(8):683-92 [PMID: 20008876]
  161. Mol Psychiatry. 2012 Jun;17(6):584-96 [PMID: 21894152]
  162. Mol Neurobiol. 2013 Dec;48(3):783-93 [PMID: 23649659]
  163. Pharmacol Rep. 2013;65(3):535-46 [PMID: 23950576]
  164. J Neural Transm Suppl. 2000;(60):277-90 [PMID: 11205147]
  165. Am J Pathol. 1999 Oct;155(4):1183-93 [PMID: 10514401]
  166. PLoS One. 2009 Jul 31;4(7):e6444 [PMID: 19649262]
  167. Pediatr Infect Dis J. 2003 Feb;22(2 Suppl):S66-74; discussion S74-5 [PMID: 12671455]
  168. Neuroscience. 2013 Dec 3;253:194-213 [PMID: 24012743]
  169. Compr Physiol. 2012 Apr;2(2):1241-67 [PMID: 23798300]
  170. Prog Brain Res. 2004;146:387-401 [PMID: 14699975]
  171. Hum Exp Toxicol. 2004 May;23(5):215-7 [PMID: 15222398]
  172. Prog Brain Res. 2004;146:151-65 [PMID: 14699963]
  173. Pharmacol Rev. 2013 Feb 27;65(2):670-709 [PMID: 23447132]
  174. Biochem Soc Trans. 2006 Aug;34(Pt 4):594-9 [PMID: 16856870]
  175. J Allergy Clin Immunol. 2006 Jan;117(1):67-71 [PMID: 16387586]
  176. Mol Biotechnol. 2002 Oct;22(2):179-89 [PMID: 12405265]
  177. Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1545-64 [PMID: 16939974]
  178. Neuroreport. 1998 Nov 16;9(16):R71-83 [PMID: 9858356]
  179. Cell Mol Life Sci. 2004 Jan;61(1):35-48 [PMID: 14704852]
  180. Inflamm Allergy Drug Targets. 2007 Jun;6(2):127-32 [PMID: 17692036]
  181. J Int Med Res. 2009 Mar-Apr;37(2):281-8 [PMID: 19383220]
  182. JAMA. 2005 Jul 20;294(3):318-25 [PMID: 16030276]
  183. Curr Pharm Des. 2005;11(8):999-1016 [PMID: 15777250]
  184. Respir Physiol Neurobiol. 2009 Nov 30;169(2):218-25 [PMID: 19703592]
  185. Am J Respir Cell Mol Biol. 2013 Apr;48(4):431-8 [PMID: 23258230]
  186. Prog Brain Res. 2004;146:347-67 [PMID: 14699973]
  187. Am J Physiol Lung Cell Mol Physiol. 2006 Sep;291(3):L447-56 [PMID: 16648236]
  188. CNS Neurol Disord Drug Targets. 2008 Feb;7(1):63-70 [PMID: 18289033]
  189. J Allergy Clin Immunol. 2006 Sep;118(3):597-605 [PMID: 16950277]
  190. Semin Perinatol. 2006 Jun;30(3):156-62 [PMID: 16813975]
  191. Biochemistry. 1998 Dec 1;37(48):16846-52 [PMID: 9836577]
  192. FASEB J. 2012 Aug;26(8):3103-17 [PMID: 22516295]
  193. Nature. 2003 Nov 6;426(6962):74-8 [PMID: 14603320]
  194. Neuropharmacology. 2014 Jan;76 Pt C:639-56 [PMID: 23602987]
  195. Respir Res. 2006 May 09;7:73 [PMID: 16684353]
  196. Am J Physiol Lung Cell Mol Physiol. 2007 Aug;293(2):L272-8 [PMID: 17575008]
  197. J Neurochem. 2007 Jul;102(2):289-305 [PMID: 17437539]
  198. Biochem Soc Trans. 2007 Apr;35(Pt 2):424-7 [PMID: 17371291]

Grants

  1. HL056470/NHLBI NIH HHS
  2. HL088029/NHLBI NIH HHS
  3. UL1 TR000135/NCATS NIH HHS
  4. R01 HL056470/NHLBI NIH HHS
  5. R01 HL088029/NHLBI NIH HHS

MeSH Term

Animals
Asthma
Brain-Derived Neurotrophic Factor
Bronchi
Calcium
Environmental Exposure
Humans
Lung
Muscle, Smooth
Pulmonary Fibrosis
Receptor, trkB
Signal Transduction

Chemicals

Brain-Derived Neurotrophic Factor
Receptor, trkB
Calcium

Word Cloud

Created with Highcharts 10.0.0airwayBDNFlungnormaldiseasesfunctionderivedneurotrophicfactorwellincludingcanpotentiallycontributeemergingneonatalasthmainflammationadditionwell-knownrolesnervoussystemincreasingrecognitionneurotrophinsbrainreceptorsexpressedperipheraltissuesthusphysiologypathophysiologyseveralrelevancefamilygrowthfactorsliesclinicaldataindicatingalteredneurotrophinlevelsrangeadultsinusitisinfluenzacancercurrentreviewfocuses1importanceexpressionsignalingmechanismsearlydevelopmentcriticalalsodisruptionprematurityinsultsinfection2nervesmodulateneurogeniccontroltonekeyaspectreflexesdysfunctionalresponsesallergic3idealocalproductionresidentcellsepitheliumsmoothmusclestructurehyperreactivityremodelingFurthermoregivenpleiotropiceffectsmaynovelappealingtherapeutictargetBrain-derivedairwaysAsthmaDevelopmentFibrosisInflammationLungNeurotrophin

Similar Articles

Cited By