Calcitonin gene-related peptide (CGRP) as hazard marker for lung injury induced by dusts

Our plain-English summary of Calcitonin gene-related peptide (CGRP) as hazard marker for lung injury induced by dusts, by Y. Morimoto, A. Ogami, H. Nagatomo, et al (Inhalation Toxicology, 2007).

The study

• Authors: Y. Morimoto, A. Ogami, H. Nagatomo, M. Hirohashi, T. Oyabu, K. Kuroda, Y. Kawanami, M. Murakami, T. Myojo, T. Higashi, I. Tanaka
• Journal: Inhalation Toxicology
• Published: 2007;19(3):283-9
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Calcitonin gene-related peptide (CGRP), which has a function as a growth factor of epithelial cells, is thought to play a role in pulmonary epithelium repair. In order to establish whether or not CGRP is associated with repair in lung damaged by dust, we examined gene expression of CGRP in the lungs of animal models exposed to different dusts. Male Wistar rats were administered 2 mg of crystalline silica, crocidolite, potassium octatitanate whisker (PT-1), and silicon carbide whisker (SiCW) suspended in saline by a single intratracheal instillation and were sacrificed at 3 d, 1 wk, 1 mo, 3 mo, and 6 mo of recovery time. Pathological findings of advanced pulmonary fibrosis were present in the rats exposed to crystalline silica and crocidolite through the experiment, whereas findings of mild or reversible pulmonary fibrosis were present in those exposed to SiCW and PT-1. The expression of CGRP in rat lung was observed by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme immunometric assay (EIA). In RT-PCR, CGRP gene expression was decreased at the interval of 3 d and 1 wk in the case of crystalline silica and crocidolite; on the other hand, it was increased at 3 d and 1 wk in SiCW and at 3 d, 1 wk, and 3 mo in PT-1-exposed rats. CGRP protein level in lungs exposed to PT-1 and SiCW was also higher than that to silica and crocidolite at 3 d of recovery time. These data suggest that CGRP is associated with repair in lung damaged by different dusts, and that CGRP could be used as a sensitive biomarker to indicate the pathogenicity of dusts.

In plain English

This was an animal experiment from Japan. The authors placed a single 2 mg dose of one of four dusts into the windpipes of male Wistar rats: crystalline silica, crocidolite, potassium octatitanate whisker (PT-1) or silicon carbide whisker (SiCW). Control rats received saline. Each group had five rats, examined from 3 days to 6 months later. The authors measured CGRP, a substance thought to help repair the lung lining. In rats given crocidolite or silica, CGRP gene activity fell at 3 days and 1 week, then returned to control levels from 1 month. In the whisker groups it rose at some time points, which differ between the abstract and the results section. At 3 days, CGRP protein was greater in the PT-1 and SiCW groups than in the silica and crocidolite groups. Rats given silica or crocidolite showed advanced lung fibrosis throughout, while those given the whiskers showed mild or reversible fibrosis. The authors concluded that CGRP is associated with repair of dust-damaged lungs and could be used as a biomarker of how harmful a dust is.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: a single intratracheal instillation of dust in rats, which were then killed and examined at set times from 3 days to 6 months
• Who was studied: Male Wistar rats, 10 weeks old, bought from Kyudo (Kumamoto, Japan); five rats per group; study by the University of Occupational and Environmental Health, Kitakyushu, Japan
• Exposure: 2 mg in 0.4 ml of one of: Min-U-Sil 5 crystalline silica, UICC crocidolite, potassium octatitanate whisker (PT-1) or silicon carbide whisker (SiCW); controls received saline
• Main results:
  • Compared with saline controls, CGRP mRNA in rat lungs decreased significantly at 3 days and 1 week in the crocidolite and crystalline silica groups
  • From 1 month of recovery, CGRP expression returned to control levels in both the crocidolite and silica groups
  • According to the results section, SiCW raised CGRP gene expression at 3 days, 1 week and 3 months, and PT-1 increased it at 1 week and 1 month (the abstract gives different time points)
  • At 3 days, CGRP protein levels were greater in lungs exposed to PT-1 and SiCW, followed by those exposed to silica and crocidolite
  • Pathological findings of advanced pulmonary fibrosis were present throughout the experiment in rats exposed to crystalline silica and crocidolite
  • Findings of mild or reversible pulmonary fibrosis were present in rats exposed to SiCW and PT-1
  • In silica-exposed rats, inflammatory cells and collagen deposition increased over the post-exposure period; no typical silicotic nodule was seen
  • In crocidolite-exposed rats, the inflammation pattern and level stayed the same over the post-exposure period
  • In SiCW- and PT-1-exposed rats, inflammatory changes gradually decreased during the experiment
• The authors' conclusion: The authors concluded that the increase of CGRP in lungs with reversible changes suggests CGRP is associated with repair in lungs damaged by different dusts, and that CGRP could be used as a biomarker of the pathogenicity of different dusts
• Limitations the authors state:
  • The authors noted that observation ended at 6 months and that, with longer observation, CGRP in the silica and crocidolite groups might shift to an increase, as a longer-term study had reported

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Epithelium, Crystalline, Crocidolite, Pulmonary Fibrosis, Biomarker.

Related studies

• Patterns of histopathological change determined by the point counting method and its application for the hazard assessment of respirable dust — A. Ogami, Y. Morimoto, et al. (2004)
• Histopathological changes in rat lung following intratracheal instillation of silicon carbide whiskers and potassium octatitanate whiskers — A. Ogami, Y. Morimoto, et al. (2007)
• Expression of Clara cell secretory protein in the lungs of rats exposed to silicon carbide whisker in vivo — Y. Morimoto, L. Ding, et al. (2003)
• Change of heme oxygenase-1 expression in lung injury induced by chrysotile asbestos in vivo and in vitro — H. Nagatomo, Y. Morimoto, et al. (2007)
• Expression of heme oxygenase-1 in the lungs of rats exposed to potassium octatitanate whiskers — Y. Obata, Y. Morimoto, et al. (2011)
• Dose-response relationship of fibrous dusts in intraperitoneal studies — M. Roller, F. Pott, et al. (1997)

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