Increased cellular senescence and vascular rarefaction exacerbate the progression of kidney fibrosis in aged mice following transient ischemic injury.
Increased cellular senescence and vascular rarefaction exacerbate the progression of kidney fibrosis in aged mice following transient ischemic injury.
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DOI：
10.1371/journal.pone.0070464
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zuk A
中科院分区：
文献类型：
--
作者：
Clements ME;Chaber CJ;Ledbetter SR;Zuk A
最近的研究结果表明，老年急性肾损伤（阿基）患者由于急性损伤的不完全恢复而进展为慢性肾病（CKD）的发生率增加。在本研究中，开发了阿基的共病模型，以更好地模拟患者人群，并研究年龄是否会加剧急性损伤后进行性肾病后遗症中发生的纤维化和炎症。对幼龄（8-10周）和老龄（46-49周）C57 BL/6小鼠进行30分钟的双侧肾缺血-再灌注（I/R）以诱导阿基。与年轻动物相比，老年动物的死亡率更高，血浆肌酐升高时间更长，这与肾小管上皮细胞增殖较少有关。再灌注后6周，基于天狼星红染色和细胞纤连蛋白、胶原蛋白III和胶原蛋白IV的免疫定位，老化肾脏中的间质纤维化更大。再灌注后6周的老年肾脏与年轻肾脏相比也表达更高水平的p53和p21，这与衰老相关（SA）β-半乳糖苷酶（细胞衰老的已知标志物）的更大增加相关。测量到F4/80+巨噬细胞和CD 4 + T淋巴细胞的较高流入，并伴随单核细胞趋化蛋白-1（MCP-1）和肿瘤坏死因子-α（TNF-α）mRNA的增加。重要的是，微血管密度显著降低，这与氧化应激标志物硝基酪氨酸的增加相关。总的来说，这些数据表明，老年动物的长期急性损伤导致慢性状态下肾脏疾病的加速进展。
Recent findings indicate that elderly patients with acute kidney injury (AKI) have an increased incidence of progression to chronic kidney disease (CKD) due to incomplete recovery from an acute insult. In the current study, a co-morbid model of AKI was developed to better mimic the patient population and to investigate whether age exacerbates the fibrosis and inflammation that develop in the sequelae of progressive kidney disease following acute injury. Young (8–10 weeks) and aged (46–49 weeks) C57BL/6 mice were subjected to 30 min bilateral renal ischemia-reperfusion (I/R) to induce AKI. The aged animals have greater mortality and prolonged elevation of plasma creatinine correlating with less tubular epithelial cell proliferation compared to the young. Six weeks post-reperfusion, interstitial fibrosis is greater in aged kidneys based on picrosirius red staining and immunolocalization of cellular fibronectin, collagen III and collagen IV. Aged kidneys 6 weeks post-reperfusion also express higher levels of p53 and p21 compared to the young, correlating with greater increases in senescence associated (SA) β-galactosidase, a known marker of cellular senescence. A higher influx of F4/80+ macrophages and CD4+ T lymphocytes is measured and is accompanied by increases in mRNA of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). Importantly, microvascular density is significantly less, correlating with an increase in nitro-tyrosine, a marker of oxidative stress. Collectively, these data demonstrate that prolonged acute injury in the aged animals results in an accelerated progression of kidney disease in a chronic state.
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影响因子：
3.3
作者：
Abdel-Kader K;Palevsky PM
通讯作者：
Palevsky PM
影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
通讯作者：
Campisi J
影响因子：
19.6
作者：
Kliem, V;Johnson, RJ;Floege, J
通讯作者：
Floege, J
DOI：
10.1097/01.asn.0000067652.51441.21
发表时间：
2003-06-01
影响因子：
13.6
作者：
Bonventre, JV
通讯作者：
Bonventre, JV
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J