Calcitonin gene-related peptide stimulates proliferation of alveolar epithelial cells View Full Text


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Article Info

DATE

2009-02-03

AUTHORS

Yukiko Kawanami, Yasuo Morimoto, Heungnam Kim, Takehiro Nakamura, Kazuhiko Machida, Takashi Kido, Etsuko Asonuma, Kazuhiro Yatera, Chiharu Yoshii, Masamitsu Kido

ABSTRACT

BackgroundAlveolar epithelial cells are known as progenitor cells for the restoration from the damage in the lung. Calcitonin gene-related peptide (CGRP) has been reported to play an important role in the proliferation of various types of epithelial and endothelial cells. We investigated the effects of CGRP on the proliferation of alveolar epithelial cells in vitro and in vivo.MethodsA549 cells were cultured in Dulbecco Modified Eagle Medium with 5% fatal bovin serum for 24 hours, then CGRP was added in vitro. The proliferation of DNA synthesis was measured using 5-bromo-2-deoxyuridine, an analog of thymidine, by enzyme-linked immunosorbent assay.As one intracellular response to CGRP, we examined activation of p44/42- extracellular signal-regulated kinase (ERK) pathway by adding CGRP, using western blotting method.Recombinant adenovirus encoding nuclear-targeted-human β-CGRP (rhCGRP) was administered into Male Wister rat (n = 5, 10 weeks old) lungs by intratracheal instillation in vivo. 7 days after the administration of CGRP, rat lungs were harvested and histological findings and immunohistochemical staining of proliferating cell nuclear antigen (PCNA) were evaluated to examine cell proliferation.ResultsIn vitro study, CGRP increased the proliferation of A549 cells in a dose and time dependent manner. CGRP8-37 (inhibitor of CGRP receptor) decreased CGRP induced proliferation of DNA synthesis. Phosphorylation of ERK pathway was observed within 15 minutes and peaked in one hour. U0126 (inhibitor of ERK pathway) decreased CGRP induced proliferation of DNA synthesis.In vivo study, histological examination of the lung indicated proliferation of alveolar epithelial cells in the rhCGRP-treated group and the nuclei of alveolar epithelial cells were positive for PCNA immunostaining.ConclusionIn this study, we conclude that CGRP stimulates proliferation of human alveolar epithelial cells in vivo and in vitro. More... »

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http://scigraph.springernature.com/pub.10.1186/1465-9921-10-8

DOI

http://dx.doi.org/10.1186/1465-9921-10-8

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https://app.dimensions.ai/details/publication/pub.1041376824

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19192276


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41 CGRP8-37
42 ConclusionIn
43 DNA synthesis
44 Dulbecco's Modified Eagle's Medium
45 ERK pathway
46 Eagle's medium
47 MethodsA549 cells
48 Modified Eagle Medium
49 PCNA
50 ResultsIn vitro studies
51 U0126
52 Western blotting method
53 activation
54 adenovirus
55 administration
56 administration of CGRP
57 alveolar epithelial cells
58 analog of thymidine
59 analogues
60 antigen
61 blotting method
62 calcitonin gene-related peptide
63 cell nuclear antigen
64 cell proliferation
65 cells
66 damage
67 days
68 dependent manner
69 dose
70 effect
71 effect of CGRP
72 endothelial cells
73 enzyme-linked immunosorbent
74 epithelial cells
75 examination
76 findings
77 gene-related peptide
78 group
79 histological examination
80 histological findings
81 hours
82 human alveolar epithelial cells
83 immunohistochemical staining
84 immunosorbent
85 important role
86 instillation
87 intracellular responses
88 intratracheal instillation
89 kinase pathway
90 lung
91 manner
92 medium
93 method
94 minutes
95 nuclear antigen
96 nucleus
97 pathway
98 peptides
99 phosphorylation
100 progenitor cells
101 proliferation
102 rat lung
103 recombinant adenovirus
104 response
105 restoration
106 role
107 serum
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