Pirfenidone suppresses MAPK signalling pathway to reverse epithelial-mesenchymal transition and renal fibrosis

Nephrology ◽  
2017 ◽  
Vol 22 (8) ◽  
pp. 589-597 ◽  
Author(s):  
Zhenzhen Li ◽  
Xianghua Liu ◽  
Baoying Wang ◽  
Yali Nie ◽  
Jianguo Wen ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Signalling Pathway ◽  
Mesenchymal Transition ◽  
Mapk Signalling Pathway ◽  
Mapk Signalling

scholarly journals MiR-199a-3p/5p participate in TGF-β and EGF induced EMT in pterygium by targeting DUSP5/MAP3K11

2020 ◽  
Author(s):  
Siying He ◽  
Yifang Huang ◽  
Shiqi Dong ◽  
Chen Qiao ◽  
Guohua Yang ◽  
...  
Keyword(s):  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Cell Model ◽  
Luciferase Reporter ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Mapk Signalling Pathway ◽  
Mapk Signalling ◽  
Emt Markers ◽  
Dual Luciferase Reporter Assay

Abstract Background: Recently, it has been reported that miRNA is correlated with pterygium, however its exact mechanism in pterygium is unrevealed and require further investigation. Methods: The differential expression of miRNA in pterygium was profiled using microarray and validated with quantitative real-time PCR (qRT-PCR). Human conjunctival epithelial cells (HCEs) were cultured and treated with TGF-b and EGF. Western blot and immunohistochemistry were carried out to detect epithelial-mesenchymal transition (EMT) markers. Wound healing and transwell assay were used to determine cell migration ability, while apoptosis was determined by flow cytometry. The target genes of miR-199a were confirmed by the dual-luciferase reporter assay. Results: TGF-b and EGF induced EMT in HCEs to mimic the pathogenesis of pterygium. MiR-199a-3p and miR-199a-5p induced EMT in HCEs, whose respectively downstream targets DUSP5 and MAP3K11 hindered EMT in EMT-HCEs in turn. TGF-b and EGF induced EMT promotion and target genes suppression, could be promoted by miR-199a-3p and miR-199a-5p, while impeded by miR-199a-3p and miR-199a-5p inhibitors. The expression levels of miR-199a and target genes were further validated in pterygium tissues, which were consistent the results in cell model. Bioinformatics analysis indicated the miR-199a-3p/5p-DUSP5/MAP3K11 was belong to MAPK signalling pathway in pterygium. Conclusions: TGF-b and EGF probably induced EMT of HCEs through miR-199a-3p/5p-DUSP5/MAP3K11 axis, which explained the pathogenesis of EMT in pterygium and might provide new targets for pterygium prevention and therapy.

Carvacrol Ameliorates Transforming Growth Factor-β1-Induced Extracellular Matrix Deposition and Reduces Epithelial-Mesenchymal Transition by Regulating The Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway In Hk-2 Cells

2021 ◽  
Vol 19 (4) ◽  
pp. 501-507
Author(s):  
Yunhe Gu ◽  
Peiyao Guo ◽  
Guangbiao Xu
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β1 ◽  
Mesenchymal Transition ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition ◽  
Dose Dependent

Transforming growth factor-β1 promotes excessive extracellular matrix deposition and epithelial-mesenchymal transition of tubular epithelial cells, thus stimulating the progression of renal fibrosis. Carvacrol has been shown to alleviate cardiac and liver fibrosis and attenuate renal injury. However, the role of carvacrol on renal fibrosis has not been examined. First, measurements using Cell Counting Kit-8 showed that carvacrol reduced cell viability of tubular epithelial cell line HK-2 in a dose-dependent fashion. Second, transforming growth factor-β1 induced excessive extracellular matrix deposition in HK-2 cells with enhanced collagen I, collagen IV, and fibronectin expression. However, carvacrol decreased the expression of collagen I, collagen IV in a dose-dependent manner and fibronectin to attenuate the extracellular matrix deposition in HK-2. Third, carvacrol attenuated TGF-β1-induced decrease of E-cadherin and increase of snail, vimentin, and alpha-smooth muscle actin in HK-2 cells. Transforming growth factor-β1-induced increase in PI3K and AKT phosphorylation in HK-2 were also reversed by carvacrol. Collectively, carvacrol ameliorates renal fibrosis through inhibition of transforming growth factor-β1-induced extracellular matrix deposition and epithelial-mesenchymal transition of HK-2 cells, providing potential therapy for the treatment of renal fibrosis.

scholarly journals The Expression of TRIM6 Activates the mTORC1 Pathway by Regulating the Ubiquitination of TSC1-TSC2 to Promote Renal Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Weiwei Liu ◽  
Yang Yi ◽  
Chuanfu Zhang ◽  
Baojuan Zhou ◽  
Lin Liao ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Diseases ◽  
Mtor Pathway ◽  
Mesenchymal Transition ◽  
Regulatory Pathways ◽  
Mtorc1 Pathway ◽  
Hk2 Cells

Renal fibrosis is considered as the final pathway of all types of kidney diseases, which can lead to the progressive loss of kidney functions and eventually renal failure. The mechanisms behind are diversified, in which the mammalian target of rapamycin (mTOR) pathway is one of the most important regulatory pathways that accounts for the disease. Several processes that are regulated by the mTOR pathway, such as autophagy, epithelial-mesenchymal transition (EMT), and endoplasmic reticulum (ER) stress, are tightly associated with renal fibrosis. In this study, we have reported that the expression of tripartite motif-containing (TRIM) protein 6, a member of TRIM family protein, was highly expressed in renal fibrosis patients and positively correlated with the severity of renal fibrosis. In our established in vitro and in vivo renal fibrosis models, its expression was upregulated by the Angiotensin II-induced nuclear translocation of nuclear factor-κB (NF-κB) p50 and p65. In HK2 cells, the expression of TRIM6 promoted the ubiquitination of tuberous sclerosis proteins (TSC) 1 and 2, two negative regulators of the mTORC1 pathway. Moreover, the knockdown of TRIM6 was found efficient for alleviating renal fibrosis and inhibiting the downstream processes of EMT and ER in both HK2 cells and 5/6-nephrectomized rats. Clinically, the level of TRIM6, TSC1/2, and NF-κB p50 was found closely related to renal fibrosis. As a result, we have presented the first study on the role of TRIM6 in the mTORC1 pathway in renal fibrosis models and our findings suggested that TRIM6 may be a potential target for the treatment of renal fibrosis.

scholarly journals SL4, a chalcone-based compound, induces apoptosis in human cancer cells by activation of the ROS/MAPK signalling pathway

2015 ◽  
Vol 48 (6) ◽  
pp. 718-728 ◽  
Author(s):  
L.-H. Wang ◽  
H.-H. Li ◽  
M. Li ◽  
S. Wang ◽  
X.-R. Jiang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Signalling Pathway ◽  
Mapk Signalling Pathway ◽  
Human Cancer Cells ◽  
Mapk Signalling
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