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.
Highlights
Alveolar epithelial cells are known as progenitor cells for the restoration from the damage in the lung
In this study, we conclude that Calcitonin gene-related peptide (CGRP) stimulates proliferation of human alveolar epithelial cells in vivo and in vitro
On the basis of our hypothesis that CGRP proliferates alveolar epithelial cells, we have examined the effects of CGRP on the proliferation of alveolar epithelial cells and extracellular signal-regulated kinase (ERK) signalling pathway as one of the cell proliferation pathways in vitro and in vivo
Summary
Alveolar 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. Alveolar epithelial type II cells are known as progenitor cells in the lung to regenerate and restore the damage. Calcitonin gene-related peptide (CGRP) is 37-amino acid neuropeptide found among neuroendocrine cells, sensory C fibers, blood vesssels and lymphoid tissues in the normal lung [1,2]. In addition to the function of vasodilatation [3], bronchial protection [4], regulatory function of macrophages [5] and regulation of airway responsiveness [6], CGRP has been reported to play a role in proliferation of epithelial and endothelial cells of various types, such as human endothelial cells [7], tracheal epithelial cells [8,9], retinal pigment epithelial cells [10] and thymic epithelial cells [11].
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