Pozzolini Marina, Scarfì Sonia, Gallus Lorenzo, Ferrando Sara, Cerrano Carlo, Giovine Marco
Department of Earth, Environment and Life Sciences (DiSTAV), University of Genova, 16132 Genoa, Italy
Department of Earth, Environment and Life Sciences (DiSTAV), University of Genova, 16132 Genoa, Italy.
J Exp Biol. 2017 Nov 1;220(Pt 21):4007-4015. doi: 10.1242/jeb.166405.
Exposure to crystalline silica particles causes silicosis, an occupational disease leading to an overproduction of collagen in the lung. The first step of this pathology is characterized by the release of inflammatory mediators. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine directly involved in silica-induced pulmonary fibrosis. The marine demosponge is able to incorporate silica grains and partially dissolve the crystalline forms apparently without toxic effects. In the present work, tissue explants were treated with fine quartz dust and the expression level of fibrogenic genes was assayed by qPCR, demonstrating an overexpression of a fibrillar and a non-fibrillar collagen and of prolyl-4-hydroxylase enzyme. The deposition of new collagen could also be documented in quartz-treated sponge explants. Furthermore, TNF pro-inflammatory cytokine overexpression and involvement in silica-induced sponge collagen biosynthesis was demonstrated in quartz-treated explants as compared with controls by means of specific TNF inhibitors affecting the fibrogenic gene response. As no documentable detrimental effect was observed in treated explants, we conclude that the unique quartz engulfment and erosion is physiological and beneficial to the animal, leading to new collagen synthesis and strengthening of the body stiffness. Thus, we put forward the hypothesis that an ancient physiological behaviour from the lowest of the Metazoa, persisting through evolution via the same molecular mediators such as TNF, may have become the cause of disease in the specialized tissues of higher animals such as mammals.
接触结晶二氧化硅颗粒会导致矽肺病，这是一种职业病，会导致肺部胶原蛋白过度产生。这种病理过程的第一步以炎症介质的释放为特征。肿瘤坏死因子（TNF）是一种促炎细胞因子，直接参与二氧化硅诱导的肺纤维化。海洋海绵能够摄取二氧化硅颗粒并部分溶解结晶形式，显然没有毒性作用。在本研究中，用细石英粉尘处理组织外植体，并通过qPCR检测纤维化基因的表达水平，结果表明一种纤维状和一种非纤维状胶原蛋白以及脯氨酰-4-羟化酶的表达上调。在石英处理的海绵外植体中也可以记录到新胶原蛋白的沉积。此外，与对照组相比，通过影响纤维化基因反应的特异性TNF抑制剂，在石英处理的外植体中证明了TNF促炎细胞因子的表达上调及其参与二氧化硅诱导的海绵胶原蛋白生物合成。由于在处理过的外植体中未观察到明显的有害影响，我们得出结论，独特的石英吞噬和侵蚀是生理性的，对动物有益，导致新胶原蛋白合成并增强身体硬度。因此，我们提出一个假设，即后生动物中最原始的一种古老生理行为，通过TNF等相同分子介质在进化过程中持续存在，可能已成为高等动物（如哺乳动物）特化组织中疾病的病因。
