Bataille Aurélien, Galichon Pierre, Ziliotis Marie-Julia, Sadia Iman, Hertig Alexandre
Department of Anesthesia and Intensive Care, Groupe Hospitalier Universitaire Saint-Louis-Lariboisière-Fernand-Widal, 75010, Paris, France.
Inserm UMR_S 1155, "Rare and common kidney diseases, matrix remodelling and tissue repair", Hôpital Tenon, 75020, Paris, France.
Crit Care. 2015 Oct 15;19:358. doi: 10.1186/s13054-015-1068-5.
Epigenetics is the study of how cells, organs, and even individuals utilize their genes over specific periods of time, and under specific environmental constraints. Very importantly, epigenetics is now expanding into the field of medicine and hence should provide new information for the development of drugs. Bomsztyk and colleagues have detected major epigenetic changes occurring in several organs as early as 6 h after the onset of a mouse model of multiple organ dysfunction syndrome induced by Staphylococcus aureus lung injury. Decrease in mRNA of key genes involved in endothelial function was found to be associated with (and potentially explained by) a decrease in permissive histone marks, while repressive marks were unchanged. We discuss here the limitations of a whole-organ as opposed to a cell-specific approach, the nature of the controls that were chosen, and the pitfalls of histone modifications as a cause of the eventual phenotype. While the use of 'epidrugs' is definitely welcome in the clinic, how and when they will be used in sepsis-related multiple organ dysfunction will require further experimental studies.
表观遗传学研究的是细胞、器官乃至个体如何在特定时间段以及特定环境限制下利用自身基因。非常重要的是，表观遗传学如今正扩展到医学领域，因此应该能为药物研发提供新信息。博姆斯蒂克及其同事早在金黄色葡萄球菌肺损伤诱导的多器官功能障碍综合征小鼠模型发病后6小时，就检测到了多个器官中发生的主要表观遗传变化。发现参与内皮功能的关键基因的mRNA减少与允许性组蛋白标记的减少相关（并可能由此解释），而抑制性标记则未改变。我们在此讨论与细胞特异性方法相对的全器官方法的局限性、所选择对照的性质以及组蛋白修饰作为最终表型原因的陷阱。虽然“表观遗传药物”在临床上肯定是受欢迎的，但它们将如何以及何时用于脓毒症相关的多器官功能障碍还需要进一步的实验研究。
