scholarly journals Expression of the Matrix Metalloproteinases and the Tissue Inhibitor of Metalloproteinase Factors are Affected by Tetramethylpyrazine Treatment in a Renal Interstitial Fibrosis Rat Model

2014 ◽  
Vol 23 (3) ◽  
pp. 309-316 ◽  
Author(s):  
Jianzhi Li ◽  
Jiangdong Yu ◽  
Yuming Liu ◽  
Li Hu ◽  
Bo Yang ◽  
...  
2017 ◽  
Vol 16 (10) ◽  
pp. 2461-2468
Author(s):  
Wei Shui ◽  
Gang Luo ◽  
Bo Qiao ◽  
Weidong Ni ◽  
Shuquan Guo

Purpose: To investigate the therapeutic effect of glucosamine cyclohexyl ester on osteoarthritis (OA) in a rat model.Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were used to analyze the effect of glucosamine cyclohexyl ester on changes in mRNA and protein expressions of matrix metalloproteinase and tissue inhibitor of metalloproteinases-1 in isolated rat chondrocytes, and in a rat model of OA. The rat model of OA was prepared by injecting monoiodoacetate to Sprague-Dawley rats via intra-articular route.Results: Treatment of the chondrocytes with glucosamine cyclohexyl ester for 48 h prevented interleukin-1 β (IL-1β)-mediated increases in mRNA and protein  expressions in matrix metalloproteinases-1, -3 and -13, and also blocked IL-1β-induced decreases in mRNA and protein expressions of tissue inhibitor of metalloproteinase-1. Glucosamine cyclohexyl ester treatment also blocked the onset of morphological changes such as irregular surface, adhesion of tissues andpresence of osteophytes in the femoral condyle surface of the OA rats. Mankin score for control, OA and glucosamine cyclohexyl ester treatment groups were 0.98 ± 0.15, 8.35 ± 0.88 and 2.39 ± 0. 67 (p = 0.002), respectively. Treatment of OA rats with glucosamine cyclohexyl ester also inhibited increases in the activities of matrix metalloproteinases-1, -3 and -13, and decreases of tissue inhibitor of metalloproteinase-1 mRNA and protein expressions. Treatment of chondrocytes and OA rats with IL-1β caused no significant changes in the levels of H3K27 and H4K8.Conclusion: These results show that glucosamine cyclohexyl ester prevents OA by targeting the expressions of matrix metalloproteinases-1, -3 and -13 and tissue inhibitor of metalloproteinases-1.Keywords: Metalloproteinases, Interleukin, Mankin score, Osteoarthritis, Cartilage


2017 ◽  
Vol 119 (2) ◽  
pp. 2200-2211 ◽  
Author(s):  
Gui‐Hong Zheng ◽  
Yong‐Jian Wang ◽  
Xin Wen ◽  
Xin‐Rui Han ◽  
Min Shen ◽  
...  

Author(s):  
Liming Guo ◽  
Kuibi Tan ◽  
Qun Luo ◽  
Xu Bai

Diabetic nephropathy (DN) is the most common complication of diabetes and is prone to kidney failure. Dihydromyricetin (DHM) has been reported to have a variety of pharmacological activities. This study aims to explore the effect of DHM on DN and the underlying molecular mechanism. An in vivo DN rat model was established. The degree of renal interstitial fibrosis (RIF) was detected by hematoxylin-eosin (HE) staining, Masson's trichrome staining, and immunohistochemistry (IHC). In vitro, NRK-52E cells were divided into four groups: normal glucose (NG), high glucose (HG), HG+DHM, and HG+rapamycin (autophagy inhibitor). The levels of autophagy- and fibrosis-related proteins were analyzed by western blotting. The expression of miR-155-5p and phosphatase and tensin homolog deleted on chromosome ten (PTEN) and their relationship were assessed by quantitative reverse transcription (qRT)-PCR and dual luciferase reporter gene assay. Our results showed that RIF was increased in DN rat model and in HG-induced NRK-52E cells. DHM treatment attenuated the increased RIF and also increased autophagy. MiR-155-5p expression was increased, while PTEN expression was decreased in DN rat and cell model, and DHM reversed both effects. Dual luciferase assay showed that PTEN was the target gene of miR-155-5p. DHM inhibited HG-induced fibrosis and promoted autophagy by inhibiting miR-155-5p expression in NRK-52E cells. In addition, DHM promoted autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. In conclusion, DHM promotes autophagy and attenuates RIF by regulating the miR-155-5p/PTEN signaling and PI3K/AKT/mTOR signaling pathway in DN.


Life Sciences ◽  
2019 ◽  
Vol 233 ◽  
pp. 116666
Author(s):  
Zhen-Zhen Qiu ◽  
Ji-Ming He ◽  
Hao-Xiang Zhang ◽  
Zuo-Hua Yu ◽  
Zhi-Wei Zhang ◽  
...  

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