Global transcriptomic changes occur in aged mouse podocytes.
Global transcriptomic changes occur in aged mouse podocytes.
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DOI：
10.1016/j.kint.2020.05.052
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发表时间：
2020-11
影响因子：
19.6
通讯作者：
Shankland SJ
中科院分区：
文献类型：
--
作者：
Wang Y;Eng DG;Kaverina NV;Loretz CJ;Koirala A;Akilesh S;Pippin JW;Shankland SJ
随着年龄的增长，肾小球足细胞经历结构和功能的改变，这增加了衰老肾脏对叠加肾小球疾病后更糟糕结果的易感性。为了描述老年小鼠足细胞的转录变化，对来自多个幼龄小鼠（2至3个月）和老年小鼠（22至24个月，相当于70多岁的人类）的报告标记（tdTomato）足细胞的分离群体进行了RNA-seq。在2494个差异表达基因中，1219个在老年足细胞中较高，1275个较低。通路富集表明，衰老足细胞中增加的主要生物学过程包括免疫应答、非编码RNA代谢、基因沉默和MAP激酶信号传导。相反，衰老的足细胞表现出发育、形态发生和代谢过程的下调。典型足细胞标记基因在衰老足细胞中表达下降，凋亡和衰老基因的增加为衰老过程中足细胞的逐渐丧失提供了一种机制。此外，我们揭示了足细胞自分泌信号网络的畸变，确定了老年足细胞中受干扰的顶级转录因子，并发现了可能促进足细胞健康衰老的候选基因调节。衰老的转录特征不同于其他肾脏疾病。因此，我们的研究为足细胞衰老过程本身的生物标志物发现和分子靶向提供了见解。
Glomerular podocytes undergo structural and functional changes with advanced age, that increase susceptibility of aging kidneys to worse outcomes following superimposed glomerular diseases. To delineate transcriptional changes in podocytes in aged mice, RNA-seq was performed on isolated populations of reporter-labeled (tdTomato) podocytes from multiple young (two to three months) and advanced aged mice (22 to 24 months, equivalent to 70 plus year old humans). Of the 2,494 differentially expressed genes, 1,219 were higher and 1,275 were lower in aged podocytes. Pathway enrichment showed that major biological processes increased in aged podocytes included immune responses, non-coding RNA metabolism, gene silencing and MAP kinase signaling. Conversely, aged podocytes showed downregulation of developmental, morphogenesis and metabolic processes. Canonical podocyte marker gene expression decreased in aged podocytes, with increases in apoptotic and senescence genes providing a mechanism for the progressive loss of podocytes seen with aging. In addition, we revealed aberrations in the podocyte autocrine signaling network, identified the top transcription factors perturbed in aged podocytes, and uncovered candidate gene modulations that might promote healthy aging in podocytes. The transcriptional signature of aging is distinct from other kidney diseases. Thus, our study provides insights into biomarker discovery and molecular targeting of the aging process itself within podocytes.
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影响因子：
82.9
作者：
通讯作者：
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影响因子：
4.6
作者：
Chozinski TJ;Mao C;Halpern AR;Pippin JW;Shankland SJ;Alpers CE;Najafian B;Vaughan JC
通讯作者：
Vaughan JC
DOI：
10.1152/ajprenal.00255.2017
发表时间：
2017-09-01
影响因子：
4.2
作者：
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通讯作者：
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影响因子：
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通讯作者：
Pandolfi PP
影响因子：
30.8
作者：
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通讯作者：
Califano, Andrea