Downregulation of lncRNA MALAT1 contributes to renal functional improvement after duodenal-jejunal bypass in a diabetic rat model
Downregulation of lncRNA MALAT1 contributes to renal functional improvement after duodenal-jejunal bypass in a diabetic rat model
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lncRNA MALAT1 的下调有助于糖尿病大鼠模型十二指肠空肠旁路术后肾功能的改善
DOI：
10.1007/s13105-018-0636-y
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发表时间：
2018
影响因子：
3.4
通讯作者：
Hu San yuan
中科院分区：
文献类型：
--
作者：
Wu Dong;Cheng Yu gang;Huang Xin;Zhong Ming wei;Liu Shao zhuang;Hu San yuan
据报道，减肥手术后肾功能有所改善，但其机制尚未得到充分研究。为了研究长链非编码RNA (lncRNA) MALAT1是否介导十二指肠空肠搭桥（DJB）术后糖尿病肾病的改善，将大鼠随机分为4组：糖尿病（DM）组、DM合并DJB手术组、DM合并假手术组和健康对照组。测定摄食量、体重、口服糖耐量试验（OGTT）、尿白蛋白排泄率（UAER）、肾小球滤过率（GFR），并行肾切片组织学检查。在体外研究中，转染MALAT1 siRNA后，在不同葡萄糖浓度下培养HK-2细胞。采用qRT-PCR和/或ELISA检测大鼠肾组织或HK-2细胞系中MALAT1、SAA3、IL-6、TNF-α的表达水平。结果显示，DJB手术改善了糖尿病大鼠的肾功能，改善了UAER和GFR，减轻了肾小球肥大。DJB后肾组织中MALAT1及其下游靶点SAA3的表达显著下调，从而降低促炎细胞因子IL-6和TNF-α的表达。在HK-2细胞系中敲低MALAT1进一步证实了在低糖和高糖条件下，MALAT1都能调节SAA3、IL-6和TNF-α的表达水平。我们的研究结果表明，MALAT1通过调节其下游靶点SAA3、IL-6和TNF-α参与DJB后肾功能的改善。
Ameliorated renal function has been reported after bariatric surgery, but the mechanisms underlying this phenomenon are not well-studied. To investigate whether the long non-coding RNA (lncRNA) MALAT1 mediates the amelioration of diabetic nephropathy after duodenal-jejunal bypass (DJB) surgery, rats were assigned randomly into four groups: diabetic (DM) group, DM with DJB surgery group, DM with sham surgery group, and healthy control group. Food intake, body weight, oral glucose tolerance test (OGTT), urine albumin excretion rate (UAER), and glomerular filtration rate (GFR) were measured and histological examination of renal sections was performed. For in vitro study, HK-2 cells were cultured under various glucose concentrations following MALAT1 siRNA transfection. Expression levels of MALAT1, SAA3, IL-6, and TNF-α in rat renal tissues or HK-2 cell lines were evaluated by qRT-PCR and/or ELISA. Results showed DJB surgery improved the renal function of diabetic rats, as indicated by ameliorated UAER and GFR and attenuated glomerular hypertrophy. Expression of MALAT1 and its downstream target SAA3 was significantly downregulated in renal tissues after DJB, which in turn decreased the expression of the pro-inflammatory cytokines IL-6 and TNF-α. Knockdown of MALAT1 in HK-2 cell lines further confirmed that expression levels of SAA3, IL-6, and TNF-α were regulated by MALAT1 under both low- and high-glucose conditions. Our findings suggest that MALAT1 is implicated in the improvement of renal function after DJB through regulation of its downstream targets SAA3, IL-6, and TNF-α.