LncRNA TUG1 inhibits the proliferation and fibrosis of mesangial cells in diabetic nephropathy via inhibiting the PI3K/AKT pathway
LncRNA TUG1 inhibits the proliferation and fibrosis of mesangial cells in diabetic nephropathy via inhibiting the PI3K/AKT pathway
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LncRNA TUG1通过抑制PI3K/AKT通路抑制糖尿病肾病系膜细胞增殖和纤维化
DOI：
10.26355/eurrev_201909_18867
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Mei, C-L
中科院分区：
文献类型：
--
作者：
Zang, X-J;Li, L.;Mei, C-L
目的：为探讨长链非编码RNA（lncRNA）TUG 1在糖尿病肾病（DN）发生、发展中的作用及其机制，采用链脲佐菌素（STZ）建立大鼠糖尿病（DM）模型。通过定量真实的时间聚合酶链反应（qRT-PCR）测定DM大鼠和对照大鼠中TUG 1和磷脂酰肌醇3-激酶（PI 3 K）/蛋白激酶B（AKT）途径中相关基因的体内水平。检测糖尿病大鼠和对照组大鼠肾重、24 h尿蛋白定量、血尿素氮和血肌酐水平。肾小球系膜细胞进行高水平葡萄糖诱导。还测定了系膜细胞中TUG 1和PI3K/AKT通路中相关基因的相对水平。采用CCK-8法和5-乙炔基-2'-脱氧尿苷（EdU）法检测TUG 1对高糖诱导的系膜细胞增殖能力的调节作用。结果：糖尿病大鼠和高糖诱导的系膜细胞TUG 1表达下调，糖尿病大鼠和高糖诱导的系膜细胞TUG 1表达下调，糖尿病大鼠和高糖诱导的系膜细胞TUG 1表达下调。与对照组相比，糖尿病大鼠的肾重、24 h尿蛋白、血尿素氮和血清肌酐水平均升高，而体内TUG 1过表达后这些指标均显著降低。此外，TUG 1的过表达下调了TGF-β 1、FN和COL-IV的表达，并抑制了PI3K/AKT通路的激活。TUG 1过表达可通过抑制PI3K/AKT信号通路抑制系膜细胞增殖和ECM积聚。
OBJECTIVE: To elucidate the potential function of long non-coding RNA (lncRNA) TUG1 in the progression of diabetic nephropathy (DN) and the underlying mechanism.MATERIALS AND METHODS: Rat diabetes mellitus (DM) model was established by streptozocin (STZ) administration. In vivo levels of TUG1 and relative genes in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in DM rats and control rats were determined by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, levels of kidney weight, 24 h-urine protein, blood urea nitrogen and serum creatinine in DM rats and controls were detected. Mesangial cells were subjected to induction of high-level glucose. Relative levels of TUG1 and relative genes in the PI3K/AKT pathway in mesangial cells were determined as well. Through Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay, the regulatory effect of TUG1 on the proliferative ability of mesangial cells induced with high-level glucose was evaluated. Finally, expression changes in the PI3K/AKT pathway and extracellular matrix (ECM)-related genes in mesangial cells were determined.RESULTS: TUG1 was downregulated in DM rats and mesangial cells induced with high-level glucose. Compared with controls, DM rats presented higher levels of kidney weight, 24 h-urine protein, blood urea nitrogen and serum creatinine, which were markedly reduced after TUG1 overexpression in vivo. Moreover, overexpression of TUG1 downregulated TGF-beta 1, FN, and COL-IV, and inhibited the activation of the PI3K/AKT pathway.CONCLUSIONS: TUG1 is downregulated in DN. The overexpression of TUG1 could suppress the proliferation and ECM accumulation of mesangial cells via inhibiting the PI3K/AKT pathway.