An In vivo Immunohistochemical Study on MacroH2A.1 in Lung and Lymph-Node Tissues Exposed to an Asbestiform Fiber

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Author(s): Carla Loreto*, Claudia Lombardo, Rosario Caltabiano, Caterina Ledda, Maria Hagnas, Vera Filetti, Venerando Rapisarda.

Journal Name: Current Molecular Medicine

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Abstract:

Aims: The aim of this study was to investigate MacroH2A.1 immunoexpression in tissues of sheep exposed to FE.

Background: The correlation between asbestiform fibers, lung cancer, pleural mesothelioma and other lung diseases is already well established as the pathophisiological respiratory mechanisms involved by inhalation of Fluoro-edenite (FE). The latter is represented by cell proliferation and inducing release of growth factors, cytokines and reactive oxygen and nitrite species, with DNA damage that cause chronic inflammation and carcinogenesis. MacroH2A.1, and histone variant, seems to play a role in sensing the metabolic state of the cell and linking it with chromatin. Physiologically, MacroH2A.1 is expressed at low levels in stem cells and it became upregulated during differentiation, preventing reprogramming of induced pluripotent stem cells and after nuclear transfer. In particular, MacroH2A.1 has been shown to explicate a potent antitumor mechanism in vivo as it results upregulated in senescent cells determining a permanent growth-arrest.

Objective: Evaluate the possible role the histone variant in the organism response to deep insight the mechanisms of toxicity and the cellular response to FE.

Methods: Lung and lymph nodes of exposed sheep were selected. Samples were processed for histological and immunihistochemical evaluations. Densitometric, morphometric and statistical analysis were conducted.

Results: Tissue sections of FE exposed sheep demonstrated an overexpression of MacroH2A.1 vs unexposed samples. The data suggest an involvement of these molecule in the cellular response triggered by FE directed exposure.

Conclusion: In this contest, MacroH2A.1 overexpression supports its function as an epigenetic stabilizer that helps to establish and maintain differentiated states.

Keywords: Lung, Asbestos, Cancer, Tumor, H2AFY, Core histone Macro-H2A.1

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1566524020666200220130023
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