Background: 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.
Methods: A549 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 beta-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.
Results: In 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.
Conclusion: In this study, we conclude that CGRP stimulates proliferation of human alveolar epithelial cells in vivo and in vitro.
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http://dx.doi.org/10.1186/1465-9921-10-8 | DOI Listing |
Mol Ther
January 2025
Perinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address:
Exemplified by successful use in COVID-19 vaccination, delivery of modified mRNA encapsulated in lipid nanoparticles provides a framework for treating various genetic and acquired disorders. However, lipid nanoparticles that can deliver mRNA into specific lung cell types have not yet been established. Here, we sought whether poly(®-amino ester)s (PBAE) or PEGylated PBAE (PBAE-PEG) in combination with 4A3-SC8/DOPE/cholesterol/DOTAP lipid nanoparticles (LNP) could deliver mRNA into different types of lung cells in vivo.
View Article and Find Full Text PDFInt J Hyg Environ Health
January 2025
Institute of Environmental Assessment and Water Research - Spanish Research council (IDAEA-CSIC), Barcelona, 08034, Spain; Spanish Ministry of Ecological Transition, Pollution Prevention Unit, Pza. San Juan de la Cruz 10, 28071, Madrid, Spain.
Research on nanoparticle (NP) release and potential exposure can be assessed through experimental field campaigns, laboratory simulations, and prediction models. However, risk assessment models are typically designed for manufactured NP (MNP) and have not been adapted for incidental NP (INP) properties. A notable research gap is identifying NP sources and their chemical, physical, and toxicological properties, especially in real-world settings.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Lung Biology, Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden.
Particulate matter (PM) is a major component of ambient air pollution. PM exposure is linked to numerous adverse health effects, including chronic lung diseases. Air quality guidelines designed to regulate levels of ambient PM are currently based on the mass concentration of different particle sizes, independent of their origin and chemical composition.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Neonatology, Children's Hospital, Capital Institute of Pediatrics, Beijing 100020, China.
Disrupted neonatal lung alveologenesis often leads to bronchopulmonary dysplasia (BPD), the most common chronic lung disease in children. The inhibition of type 2 alveolar (AT2) cell proliferation plays an important role in the arrest of alveologenesis. However, the mechanism of AT2 cell proliferation retardation in BPD is still not fully elucidated.
View Article and Find Full Text PDFAnn Card Anaesth
January 2025
All India Institute of Medical Sciences, Raipur, Chhattisgarh, India.
Pulmonary alveolar proteinosis (PAP) is a rare pulmonary pathology characterized by the accumulation of surfactant within type II alveolar epithelial cells. Whole lung lavage is the standard treatment for pulmonary alveolar proteinosis involving a large volume of fluid is infused into one lung and subsequently retrieved while the other lung is remains ventilated. Fast-tracking a patient undergoing whole lung lavage requires vigilant monitoring of arterial blood gases, fluid status, and respiratory mechanics.
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