scholarly journals Losartan Alleviates Renal Fibrosis and Inhibits Endothelial-to-Mesenchymal Transition (EMT) Under High-Fat Diet-Induced Hyperglycemia

2018 ◽  
Vol 9 ◽  
Author(s):  
Yufeng Yao ◽  
Yong Li ◽  
Xiaofei Zeng ◽  
Zheng Ye ◽  
Xia Li ◽  
...  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Myeongjoo Son ◽  
Seyeon Oh ◽  
Ji Tae Jang ◽  
Kuk Hui Son ◽  
Kyunghee Byun

Endothelial-to-mesenchymal transition (EndMT), which is involved in the development of various cardiovascular diseases, is induced by dyslipidemia or obesity. In dyslipidemia, the increased levels of oxidized low-density lipoproteins (oxLDL) upregulated the lectin-type oxidized LDL receptor 1 (Lox-1), which then upregulated the down signaling pathways of PKC-α/MMPs/TGF-β/SMAD2 or 3 and increased the EndMT. In this study, we investigated the effect of pyrogallol-phloroglucinol-6,6-bieckol (PPB), which is a compound of Ecklonia cava (E. cava), on decreased blood pressure (BP) by attenuating the EndMT in a high-fat diet- (HFD-) fed animal model. We also investigated PPB’s attenuation effect on EndMT in oxLDL-treated mouse endothelial cells as an in vitro model. The results indicated that, in the aorta or endothelial cells of mice, the HFD or oxLDL treatment significantly increased the expression of Lox-1/PKC-α/MMP9/TGF-β/SMAD2/SMAD3. The PPB treatment significantly decreased its expression. In contrast, the HFD or oxLDL treatment significantly decreased the expression of the EC markers (PECAM-1 and vWF) while the PPB treatment significantly increased them. Moreover, the HFD or oxLDL treatment significantly increased the expression of the mesenchymal cell markers (α-SMA and vimentin) while PPB treatment significantly decreased them. PPB decreased the intima-media thickness and extracellular matrix amount of the aorta and attenuated the BP, which was increased by the HFD. In conclusion, PPB attenuated the upregulation of Lox-1/PKC-α/MMP9/TGF-β/SMAD2 and 3 and restored the EndMT in HFD-fed animals. Moreover, PPB showed a restoring effect on HFD-induced hypertension.


Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1298 ◽  
Author(s):  
Hung-Yu Lin ◽  
Feng-Sheng Wang ◽  
Ya-Ling Yang ◽  
Ying-Hsien Huang

MicroRNA-29 (miR-29) has been shown to play a critical role in reducing inflammation and fibrosis following liver injury. Non-alcoholic fatty liver disease (NAFLD) occurs when fat is deposited (steatosis) in the liver due to causes other than excessive alcohol use and is associated with liver fibrosis. In this study, we asked whether miR-29a could reduce experimental high fat diet (HFD)-induced obesity and liver fibrosis in mice. We performed systematical expression analyses of miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates subjected to HFD-induced NAFLD. The results demonstrated that increased miR-29a not only alleviated HFD-induced body weight gain but also subcutaneous, visceral, and intestinal fat accumulation and hepatocellular steatosis in mice. Furthermore, hepatic tissue in the miR-29aTg mice displayed a weak fibrotic matrix concomitant with low fibrotic collagen1α1 expression within the affected tissues compared to the wild-type (WT) mice fed the HFD diet. Increased miR-29a signaling also resulted in the downregulation of expression of the epithelial mesenchymal transition-executing transcription factor snail, mesenchymal markers vimentin, and such pro-inflammation markers as il6 and mcp1 within the liver tissue. Meanwhile, miR-29aTg-HFD mice exhibited significantly lower levels of peroxisome proliferator-activated receptor γ (PPARγ), mitochondrial transcription factor A TFAM, and mitochondria DNA content in the liver than the WT-HFD mice. An in vitro luciferase reporter assay further confirmed that miR-29a mimic transfection reduced fatty acid translocase CD36 expression in HepG2 cells. Conclusion: Our data provide new insights that miR-29a can improve HDF-induced obesity, hepatocellular steatosis, and fibrosis, as well as highlight the role of miR-29a in regulation of NAFLD.


2014 ◽  
Vol 63 (2) ◽  
pp. 158-166 ◽  
Author(s):  
Yao Dai ◽  
Philip Palade ◽  
Xianwei Wang ◽  
Federico Mercanti ◽  
Zufeng Ding ◽  
...  

Author(s):  
Xiangjie Qiu ◽  
Ousman Bajinka ◽  
Lili Wang ◽  
Guojun Wu ◽  
Yurong Tan

Abstract Background High fat diet is extensively studied to be associated with trending metabolic diseases. In addition to type 2 diabetes and hypertension, high fat diet is strongly associated with asthma and other respiratory diseases among children however, the pathogenicity regarding these pulmonary diseases begs for extensive research. This study investigated the mechanism of the epithelial-mesenchymal transition of respiratory tract, induced by changes in lung microecology with the intake of high-fat diet. 80 five-week-old C57BL6/J male mice were randomly divided into normal control group, normal hydrogen group, high-fat group and high-fat hydrogen group, making 20 mice in each group. The weight of the mice were measured on weekly basis. 6 mice from each group were executed at every second week. Blood sample was collected for lipid testing, lung tissues were collected for 16SrRNA gene sequencing, HE staining, immunofluorescence and quantitative real-time PCR (qPCR).Results Compared with the normal diet group, mice on the high-fat diet group showed increased inflammatory cell infiltration, decreased expression of e-cadherin (E-cad) and increased expression of Twist. There were significant differences in the composition of bacteria in the lung, and the expression of isocitrate lyase (ICL) gene in Pseudomonas aeruginosa , Staphylococcus aureus and Acinetobacter baumannii , which were significantly associated with asthma were seen with a significant increasing trend. After the treatment of saturated hydrogen, the changes in lung microbial population, lung tissue infiltration of inflammatory cells and the transformation of epithelial stroma caused by high-fat diet were moderately alleviated.Conclusion High fat diet can affect the process of airway epithelial stroma by altering the glyoxylate cycle of pulmonary microbes while the pathological process are alleviated by saturated hydrogen by acting on glyoxylate cycle.


2020 ◽  
Vol 142 ◽  
pp. 111108
Author(s):  
Sugyeong Ha ◽  
Min Jo Kim ◽  
Dae Hyun Kim ◽  
Byeong Moo Kim ◽  
Ki Wung Chung ◽  
...  

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