scholarly journals Gremlin Regulates Tubular Epithelial to Mesenchymal Transition via VEGFR2: Potential Role in Renal Fibrosis

2018 ◽  
Vol 9 ◽  
Author(s):  
Laura Marquez-Exposito ◽  
Carolina Lavoz ◽  
Raul R. Rodrigues-Diez ◽  
Sandra Rayego-Mateos ◽  
Macarena Orejudo ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Potential Role ◽  
Mesenchymal Transition

MKP2 inhibits TGF-β1-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells through a JNK-dependent pathway

2018 ◽  
Vol 132 (21) ◽  
pp. 2339-2355 ◽  
Author(s):  
Zhenzhen Li ◽  
Xianghua Liu ◽  
Fengyan Tian ◽  
Ji Li ◽  
Qingwei Wang ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Mitogen Activated Protein Kinase ◽  
Jnk Signaling ◽  
Mesenchymal Transition ◽  
Amino Terminal ◽  
Ureter Obstruction ◽  
Tgf Β1

Epithelial-to-mesenchymal transition (EMT) is a phenotypic conversion that plays a crucial role in renal fibrosis leading to chronic renal failure. Mitogen-activated protein kinase phosphatase 2 (MKP2) is a member of the dual-specificity MKPs that regulate the MAP kinase pathway involved in transforming growth factor-β1 (TGF-β1)-induced EMT. However, the function of MKP2 in the regulation of EMT and the underlying mechanisms are still largely unknown. In the present study, we detected the expression of MKP2 in an animal model of renal fibrosis and evaluated the potential role of MKP2 in tubular EMT induced by TGF-β1. We found that the expression of MKP2 was up-regulated in the tubular epithelial of unilateral ureter obstruction rats. Meanwhile, we also demonstrated that TGF-β1 up-regulated MKP2 expression in NRK-52E cells during their EMT phenotype acquisition. Importantly, overexpression of MKP2 inhibited c-Jun amino terminal kinase (JNK) signaling and partially reversed EMT induced by TGF-β1. Moreover, reducing MKP2 expression enhanced JNK phosphorylation, promoted the E-cadherin suppression and induced α-SMA expression and fibronectin secretion in response to TGF-β1, which could be rescued by a JNK inhibitor. These results provide the first evidence that MKP2 is a negative feedback molecule induced by TGF-β1, and MKP2 overexpression inhibits TGF-β1-induced EMT through the JNK signaling pathway. MKP2 could be a promising target to be used in gene therapy for renal fibrosis.

scholarly journals Hydroxysafflor Yellow A Ameliorates Renal Fibrosis by Suppressing TGF-β1-Induced Epithelial-to-Mesenchymal Transition

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153409 ◽  
Author(s):  
Naping Hu ◽  
Jialin Duan ◽  
Huihui Li ◽  
Yanhua Wang ◽  
Fang Wang ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Hydroxysafflor Yellow A ◽  
Mesenchymal Transition ◽  
Tgf Β1

scholarly journals Inhibition of α1‐adrenoceptor reduces TGF‐β1‐induced epithelial‐to‐mesenchymal transition and attenuates UUO‐induced renal fibrosis in mice

2020 ◽  
Vol 34 (11) ◽  
pp. 14892-14904
Author(s):  
Huiwen Ren ◽  
Shengkai Zuo ◽  
Yayan Hou ◽  
Wenlong Shang ◽  
Na Liu ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Tgf Β1

scholarly journals High-Mobility Group Nucleosome-Binding Protein 1 Mediates Renal Fibrosis Correlating with Macrophages Accumulation and Epithelial-to-Mesenchymal Transition in Diabetic Nephropathy Mice Model

2019 ◽  
Vol 44 (3) ◽  
pp. 331-343
Author(s):  
Jiali Yu ◽  
Rong Dong ◽  
Jingjing Da ◽  
Jiayu Li ◽  
Fuxun Yu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Binding Protein ◽  
High Mobility ◽  
Treated Group ◽  
High Mobility Group ◽  
Mesenchymal Transition ◽  
Collagen Expression ◽  
Nucleosome Binding

Background/Aim: Renal fibrosis is essential for the progression of diabetic nephropathy (DN). Macrophages accumulate in diabetic kidneys and are involved in epithelial-to-mesenchymal transition (EMT), a vital mechanism leading to renal fibrosis. Recently, high-mobility group nucleosome-binding protein 1(HMGN1) was documented in promoting the recruitment and activation of antigen-presenting cells. In this study, we first reported its roles in renal fibrosis and the underlying mechanism associated with macrophage filtration and EMT. Methods: Twenty C57BL/6J mice were administered streptozotocin (STZ) to induce diabetes for 6 weeks and then divided into 4 groups: normal control group; DN group; benazepril-treated group, and insulin-treated group. Blood glucose, creatinine, and albumin in urine, hematoxylin and eosin, and Sirius red staining of kidney tissues were used to assess the renal pathology. ELISA, immunochemistry, and in situ hybridization were performed to determine the expression of HMGN1, CD68, F4/80, α-smooth muscle actin, and E-cadherin. Results: The renal expression levels of HMGN1, macrophage markers, and EMT makers were increased in DN group, and insulin treatment could reduce the overexpression of these indicators with a better effect than benazepril treatment. Both treatments could not obviously ameliorate urine albumin-to-creatinine ratio, collagen expression, and renal histological changes in STZ-induced diabetic mice. Correlation analysis indicated that there was a relationship among HMGN1, macrophage markers, EMT markers, and collagen expression in DN mice. Conclusion: HMGN1 may promote macrophages accumulation and EMT, suggesting a potential therapeutic target for preventing renal fibrosis development in DN.

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