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Gene changes in response to asbestos and carbon nanotube exposure in the pleural cavity, measured using microarrays.

ABSTRACT: Exposure to asbestos fibres causes profound pathological changes in the pleural cavity and can result in the development of a fatal tumour, malignant mesothelioma (MM). Due to their structural similarities there is concern that carbon nanotubes (CNTs) may present a similar inhalation hazard. However the underlying mechanisms leading to fibre-mediated mesothelioma development are not yet fully understood. To investigate the molecular changes which occur at the mesothelium as a consequence of direct exposure to fibres, short and long asbestos fibres (SFA and LFA) and short and long CNTs (NTS and NTL) were instilled directly into the pleural cavity in mice. After 12 weeks RNA was extracted from the diaphragm and microarray analysis was performed on all of the treatment groups compared to a 0.5% BSA/saline control. Concurrent histopatholgical investigations were performed and revealed that exposure to fibres resulted in responses that were dependent upon the length of the fibres, but not on fibre type. In response to NTL and LFA there was acute inflammation and fibrosis on the parietal pleura; no inflammatory changes were detected histologically after exposure to SFA and NTS. Furthermore, changes in the mTOR signalling pathway were observed. Thus, this study served to illustrate which pathways are involved in the development of fibre-mediated toxicity, and demonstrated that pleural lesions induced by long asbestos fibres and long CNT exhibit a common pro-oncogenic molecular signature.

ORGANISM(S): Mus musculus

PROVIDER: GSE51636 | GEO | 2017/11/20

SECONDARY ACCESSION(S): PRJNA224144

REPOSITORIES: GEO

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Project description:Cotton (Gossypium hirsutum L.) fibres are specialised trichomes that extend from the seedcoat. To date only a few genes directly involved in the differentiation of these epidermal cells have been identified. We have identified a HD-ZIP transcription factor, GhHD-1, expressed in trichomes and early fibres that might play a role in cotton fibre initiation. Here we characterise GhHD-1 from G. hirsutum and show, using reporter constructs and qRT-PCR, that they are expressed predominantly in epidermal tissues during early fibre development and in other tissues bearing epidermal trichomes. GhHD-1 silencing caused reduced trichome formation and delayed the timing of fibre initiation whereas constitutive over-expression of GhHD-1 increased the number of fibres initiating on the seed, but did not affect leaf trichomes. Expression of GhHD-1 in transgenic cotton silenced for different fibre MYBs suggest that in ovules it acts downstream of GhMYB25-like. Microarray analysis of silencing and over-expression lines of GhHD-1 indicated that it potentially functions through a WRKY transcription factor and calcium-signalling pathway genes that are shared with some biotic stress reactions. Microarray analysis of 2 biological replicates each of GhHD-1 silenced and over-expression transgenic lines relative to wild-type were used to identify downstream targets of this transcription factor during early fibre development. 0 dpa (Days post anthesis) ovules from GhHD-1 silenced and over-expression lines and wild-type cotton plants were selected for RNA extraction and hybridisation on Affymetrix cotton arrays. Cotton fibre development initiates on the epidermal surface of each ovule within a cotton boll on the day of flowering and GhHD-1 has been shown to be most highly expressed at this stage (0 dpa). Ovules were obtained from 0dpa flowers for hybridisation to cotton arrays to identify genes that may be regulated by GhHD-1 during this early fibre development stage (initiation).

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Gene changes in response to asbestos and carbon nanotube exposure in the pleural cavity, measured using microarrays.

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