Stangenberg Stephanie, Chen Hui, Wong Muh Geot, Pollock Carol A, Saad Sonia
Kolling Institute, Department of Medicine, Royal North Shore Hospital and University of Sydney, St. Leonards, Sydney, New South Wales, Australia; and.
School of Medical and Molecular Biosciences, Faculty of Science, Centre for Health Technology, University of Technology, Sydney, New South Wales, Australia.
Am J Physiol Renal Physiol. 2015 Jun 1;308(11):F1189-96. doi: 10.1152/ajprenal.00638.2014. Epub 2015 Feb 4.
The role of an adverse in utero environment in the programming of chronic kidney disease in the adult offspring is increasingly recognized. The cellular and molecular mechanisms linking the in utero environment and future disease susceptibility remain unknown. Maternal smoking is a common modifiable adverse in utero exposure, potentially associated with both mitochondrial dysfunction and epigenetic modification in the offspring. While studies are emerging that point toward a key role of mitochondrial dysfunction in acute and chronic kidney disease, it may have its origin in early development, becoming clinically apparent when secondary insults occur. Aberrant epigenetic programming may add an additional layer of complexity to orchestrate fibrogenesis in the kidney and susceptibility to chronic kidney disease in later life. In this review, we explore the evidence for mitochondrial dysfunction and epigenetic modification through aberrant DNA methylation as key mechanistic aspects of fetal programming of chronic kidney disease and discuss their potential use in diagnostics and targets for therapy.
子宫内不良环境在成年后代慢性肾病编程中的作用日益受到认可。连接子宫内环境与未来疾病易感性的细胞和分子机制仍不清楚。母亲吸烟是一种常见的可改变的子宫内不良暴露，可能与后代的线粒体功能障碍和表观遗传修饰有关。虽然越来越多的研究表明线粒体功能障碍在急性和慢性肾病中起关键作用，但它可能起源于早期发育，在继发损伤发生时才在临床上显现出来。异常的表观遗传编程可能会增加一层复杂性，从而在肾脏中协调纤维生成以及在以后的生活中增加患慢性肾病的易感性。在这篇综述中，我们探讨了线粒体功能障碍和通过异常DNA甲基化进行的表观遗传修饰作为慢性肾病胎儿编程关键机制方面的证据，并讨论了它们在诊断和治疗靶点中的潜在用途。
