Effects of LncRNA MALAT1 on microangiopathy and diabetic kidney disease in diabetic rats by regulating ERK/MAPK signaling pathway

2020 ◽  
Vol 111 (2) ◽  
Author(s):  
Shaoqing Shi ◽  
Jing Yang ◽  
Wenxing Fan ◽  
Zhu Zhou ◽  
Guangmei Chen ◽  
...  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shu-Juan Xie ◽  
Li-Ting Diao ◽  
Nan Cai ◽  
Li-Ting Zhang ◽  
Sha Xiang ◽  
...  

AbstractMALAT1-associated small cytoplasmic RNA (mascRNA) is a cytoplasmic tRNA-like small RNA derived from nucleus-located long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). While MALAT1 was extensively studied and was found to function in multiple cellular processes, including tumorigenesis and tumor progression, the role of mascRNA was largely unknown. Here we show that mascRNA is upregulated in multiple cancer cell lines and hepatocellular carcinoma (HCC) clinical samples. Using HCC cells as model, we found that mascRNA and its parent lncRNA MALAT1 can both promote cell proliferation, migration, and invasion in vitro. Correspondingly, both of them can enhance the tumor growth in mice subcutaneous tumor model and can promote metastasis by tail intravenous injection of HCC cells. Furthermore, we revealed that mascRNA and MALAT1 can both activate ERK/MAPK signaling pathway, which regulates metastasis-related genes and may contribute to the aggressive phenotype of HCC cells. Our results indicate a coordination in function and mechanism of mascRNA and MALAT1 during development and progress of HCC, and provide a paradigm for deciphering tRNA-like structures and their parent transcripts in mammalian cells.


2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Li Peng ◽  
Jie Li ◽  
Yixing Xu ◽  
Yangtian Wang ◽  
Hong Du ◽  
...  

Background. p38 mitogen-activated protein kinase (MAPK) plays a crucial role in regulating signaling pathways implicated in inflammatory processes leading to diabetic nephropathy (DN). This study aimed to examine p38 MAPK activation in DN and determine whether beraprost sodium (BPS) ameliorates DN by inhibiting inflammation and p38 MAPK signaling pathway in diabetic rats.Methods. Forty male Sprague Dawley (SD) rats were randomly divided into the normal control group, type 2 diabetic group, and BPS treatment group. At the end of the 8-week experiment, we measured renal pathological changes and the activation of the p38 MAPK signaling pathway and inflammation.Result. After BPS treatment, renal function, 24-hour urine protein, lipid profiles, and blood glucose level were improved significantly; meanwhile, inflammation and the expression of p38 MAPK signaling pathway in the diabetic kidney were attenuated.Conclusions. BPS significantly prevented type 2 diabetes induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms are complicated but may be mainly attributed to the inhibition of the p38 MAPK signaling pathway and inflammation in the diabetic kidney.


2012 ◽  
Vol 47 (3) ◽  
pp. 604-614 ◽  
Author(s):  
Vivian Soetikno ◽  
Flori R. Sari ◽  
Vijayakumar Sukumaran ◽  
Arun Prasath Lakshmanan ◽  
Sayaka Mito ◽  
...  

Toxicology ◽  
2005 ◽  
Vol 209 (3) ◽  
pp. 279-287 ◽  
Author(s):  
Ruben Ruiz-Ramos ◽  
Mariano E. Cebrian ◽  
Efraín Garrido

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Tong Zhou ◽  
Lin Sun ◽  
Shuo Yang ◽  
You Lv ◽  
Yue Cao ◽  
...  

20(S)-Ginsenoside Rg3 (20(S)-Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups: control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3. Plus, the urine protein decreased in the rats with the 20(S)-Rg3 treatment. Fasting blood glucose, creatinine, total cholesterol, and triglyceride levels in the 20(S)-Rg3 treatment group were all lower than those in the diabetic group. Mechanistically, 20(S)-Rg3 dramatically downregulated the expression of TGF-β1, NF-κB65, and TNF-α in the kidney. These resulted in a significant prevention of renal damage from the inflammation. The results of the current study suggest that 20(S)-Rg3 could potentially be used as a novel treatment against DKD.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Lian-ji Zhou ◽  
Da-wei Yang ◽  
Li-Na Ou ◽  
Xing-Rong Guo ◽  
Biao-liang Wu

Background. Long noncoding RNA MALAT1 is closely related to diabetes and kidney diseases and is expected to be a new target for the diagnosis and treatment of diabetic nephropathy. Objective. This study aimed to explore the circulating expression level and significance of lncRNA Malat1 in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Methods. Quantitative real-time PCR (qPCR) was conducted to assess the expression of lncRNA Malat1 in 20 T2DM patients, 27 DKD patients, and 14 healthy controls, and then, the clinical significance was analyzed. Results. LncRNA MALAT1 expression in peripheral blood mononuclear cells (PBMC) was significantly upregulated in T2DM and DKD groups when compared to control. Pearson’s correlation analysis showed correlation of lncRNA MALAT1 levels with ACR, urine β2-microglobulin (β2-MG), urine α1-microglobulin (α1-MG), creatinine (Cr), and glycosylated hemoglobin (HbA1c), while negative with superoxide dismutase (SOD) (r=−0.388, P<0.05). Binary regression analysis showed that ACR, creatinine, α1-MG, and LncRNA Malat1 were the risk factors for diabetic nephropathy with OR value of 1.166, 1.031, 1.031, and 2.019 (P<0.05). The area under ROC curve (AUC) of DKD identified by the above indicators was 0.914, 0.643, 0.807, and 0.797, respectively. The AUC of Joint prediction probability of DKD recognition was 0.914, and the sensitivity and specificity of DKD diagnosis were 1.0 and 0.806, respectively. (Take ≥0.251 as the diagnostic cutoff point). Conclusion. LncRNA Malat1 is highly expressed in DKD patients, and the combined detection of ACR, creatinine, α1-MG, and LncRNA Malat1 with diabetes mellitus may be the best way to diagnose diabetic nephropathy.


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