Department of Bio-Medical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.
Human Anatomy, Department of Medical and Surgical Sciences and Advanced Technologies, G.F. Ingrassia, University of Catania, Catania, Italy.
Curr Mol Med. 2020;20(8):653-660. doi: 10.2174/1566524020666200220130023.
The aim of this study was to investigate MacroH2A.1 immunoexpression in tissues of sheep exposed to FE.
The correlation between asbestiform fibers, lung cancer, pleural mesothelioma, and other lung diseases is already well established as the pathophisiological pathophysiological respiratory mechanisms involved by inhalation of Fluoro-edenite (FE). The latter is represented by cell proliferation and inducing the release of growth factors, cytokines, and reactive oxygen and nitrite species, with DNA damage that causes 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.
Evaluate the possible role of the histone variant in the organism in response to deep insight understanding the mechanisms of toxicity and the cellular response to FE.
Lung and lymph nodes of exposed sheep were selected. Samples were processed for histological and immunihistochemical immunohistochemical evaluations. Densitometric, morphometric, and statistical analysis analyses were conducted.
Tissue sections of FE exposed sheep demonstrated overexpression of MacroH2A.1 vs unexposed samples. The data suggest an involvement of these this molecule in the cellular response triggered by FE directed exposure.
In this contest, MacroH2A.1 overexpression supports its function as an epigenetic stabilizer that helps to establish and maintain differentiated states.
本研究旨在探讨暴露于氟碳青霉烯（FE）的绵羊组织中 MacroH2A.1 的免疫表达。
吸入氟碳青霉烯（FE）所涉及的病理生理呼吸机制已将纤维状石棉与肺癌、胸膜间皮瘤和其他肺部疾病之间的相关性确立。后者表现为细胞增殖并诱导生长因子、细胞因子和活性氧及亚硝酸盐的释放，导致 DNA 损伤，引起慢性炎症和癌变。MacroH2A.1 是一种组蛋白变体，似乎在感知细胞的代谢状态并将其与染色质联系起来方面发挥作用。在生理上，MacroH2A.1 在干细胞中低表达，在分化过程中上调，防止诱导多能干细胞的重编程和核转移后。特别是，MacroH2A.1 已被证明在体内具有有效的抗肿瘤机制，因为它在衰老细胞中上调，导致永久性生长停滞。
评估组蛋白变体在生物体中的可能作用，以深入了解毒性机制和细胞对 FE 的反应。
选择暴露于 FE 的绵羊的肺和淋巴结。对样本进行组织学和免疫组织化学评估。进行了密度计量学、形态计量学和统计学分析。
暴露于 FE 的绵羊组织切片显示 MacroH2A.1 的过度表达与未暴露样本相比。这些数据表明，这种分子参与了 FE 暴露引发的细胞反应。
在这种情况下，MacroH2A.1 的过度表达支持其作为表观遗传稳定剂的功能，有助于建立和维持分化状态。
