非编码RNA作为早期糖尿病肾病的治疗靶点
Noncoding RNAs as therapeutic targets in early stage diabetic kidney disease.
作者信息
Kato Mitsuo
机构信息
Beckman Research Institute of City of Hope, Duarte, CA, USA.
出版信息
Kidney Res Clin Pract. 2018 Sep;37(3):197-209. doi: 10.23876/j.krcp.2018.37.3.197. Epub 2018 Sep 30.
Diabetic kidney disease (DKD) is a major renal complication of diabetes that leads to renal dysfunction and end-stage renal disease (ESRD). Major features of DKD include accumulation of extracellular matrix proteins and glomerular hypertrophy, especially in early stage. Transforming growth factor-β plays key roles in regulation of profibrotic genes and signal transducers such as Akt kinase and MAPK as well as endoplasmic reticulum stress, oxidant stress, and autophagy related to hypertrophy in diabetes. Many drugs targeting the pathogenic signaling in DKD (mostly through protein-coding genes) are under development. However, because of the limited number of protein-coding genes, noncoding RNAs (ncRNAs) including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are attracting more attention as potential new drug targets for human diseases. Some miRNAs and lncRNAs regulate each other (by hosting, enhancing transcription from the neighbor, hybridizing each other, and changing chromatin modifications) and create circuits and cascades enhancing the pathogenic signaling in DKD. In this short and focused review, the functional significance of ncRNAs (miRNAs and lncRNAs) in the early stages of DKD and their therapeutic potential are discussed.
糖尿病肾病(DKD)是糖尿病的一种主要肾脏并发症,可导致肾功能不全和终末期肾病(ESRD)。DKD的主要特征包括细胞外基质蛋白的积累和肾小球肥大,尤其是在早期阶段。转化生长因子-β在调节促纤维化基因和信号转导分子(如Akt激酶和MAPK)以及与糖尿病肥大相关的内质网应激、氧化应激和自噬中起关键作用。许多针对DKD致病信号传导的药物(主要通过蛋白质编码基因)正在研发中。然而,由于蛋白质编码基因数量有限,包括微小RNA(miRNA)和长链非编码RNA(lncRNA)在内的非编码RNA(ncRNA)作为人类疾病潜在的新药物靶点正受到越来越多的关注。一些miRNA和lncRNA相互调节(通过宿主作用、增强邻近基因的转录、相互杂交以及改变染色质修饰),并形成增强DKD致病信号传导的回路和级联反应。在这篇简短而有针对性的综述中,我们讨论了ncRNA(miRNA和lncRNA)在DKD早期阶段的功能意义及其治疗潜力。