Exposure to Multiwall Carbon Nanotubes Promotes Fibrous Proliferation by Production of Matrix Metalloproteinase-12 via NF-κB Activation in Chronic Peritonitis

Takemoto, Tsunematsu; Arakaki, Rieko; Sato, Mami; Saitō, Masako; Otsuka, Kunihiro; Furukawa, Yusuke; Taquahashi, Yuhji; Kanno, Jun; Ishimaru, Naozumi

doi:10.1016/j.ajpath.2022.07.009

Cited by 1 publication

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“…MMP12 plays a role in degrading ECM and contributing to remodeling damaged tissues. Some researchers have reported high levels of MMP12 induction in macrophages and surrounding tissues as a response to carbon-based nanomaterials [ 17 , 79 , 80 ]. In the present study, marked upregulation and time-dependent increases at both transcript and protein levels were observed, suggesting the participation of Mmp12 in the worsening of histological findings such as fibrosis, granulation, and proliferation of epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test

et al. 2023

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Despite intensive toxicological studies of carbon nanotubes (CNTs) over the last two decades, only a few studies have demonstrated their pulmonary carcinogenicities in chronic animal experiments, and the underlying molecular mechanisms are still unclear. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis using a set of lung tissues collected from rats in a 2-year study, in which lung tumors were induced by repeated intratracheal instillations of a multiwalled carbon nanotube, MWNT-7. The RNA-seq-based transcriptome identified a large number of significantly differentially expressed genes at Year 0.5, Year 1, and Year 2. Ingenuity Pathway Analysis revealed that macrophage-elicited signaling pathways such as phagocytosis, acute phase response, and Toll-like receptor signaling were activated throughout the experimental period. At Year 2, cancer-related pathways including ERBB signaling and some axonal guidance signaling pathways such as EphB4 signaling were perturbed. qRT-PCR and immunohistochemistry indicated that several key molecules such as Osteopontin/Spp1, Hmox1, Mmp12, and ERBB2 were markedly altered and/or localized in the preneoplastic lesions, suggesting their participation in the induction of lung cancer. Our findings support a scenario of inflammation-induced carcinogenesis and contribute to a better understanding of the molecular mechanism of MWCNT carcinogenicity.

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Section: Discussionmentioning

confidence: 99%