scholarly journals Disruption of E-Cadherin by Matrix Metalloproteinase Directly Mediates Epithelial-Mesenchymal Transition Downstream of Transforming Growth Factor-β1 in Renal Tubular Epithelial Cells

2009 ◽  
Vol 175 (2) ◽  
pp. 580-591 ◽  
Author(s):  
Guoping Zheng ◽  
James Guy Lyons ◽  
Thian Kui Tan ◽  
Yiping Wang ◽  
Tzu-Ting Hsu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Matrix Metalloproteinase ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β1 ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Mesenchymal Transition ◽  
Renal Tubular

IGFBP7 regulates sepsis-induced epithelial-mesenchymal transition through ERK1/2 signaling

2019 ◽  
Vol 51 (8) ◽  
pp. 799-806
Author(s):  
Xiaolin Wang ◽  
Yan Li ◽  
Zhenzhen Zhao ◽  
Yan Meng ◽  
Jinjun Bian ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Mesenchymal Transition ◽  
Renal Tubular ◽  
Hk2 Cells ◽  
Tgf Β1

Abstract The epithelial-mesenchymal transition (EMT) process results in fibrosis of renal tubular epithelial cells and is of great importance in the development of acute kidney injury (AKI). Urinary IGF-binding protein-7 (IGFBP7) was obviously increased in AKI and is considered to be a biomarker for AKI. However, whether it has an effect on the inhibition of lipopolysaccharide (LPS)-induced EMT in human HK2 cells and on that of cecal ligation and puncture (CLP)-induced EMT in human HK2 cells and in mice remains to be elucidated. Western blot analysis was performed to examine the phosphorylation of ERK1/2 level and expressions of IGFBP7, ERK1/2, EMT markers, such as E-cadherin, α-SMA, and vimentin, and EMT regulatory factors, such as Snail, transforming growth factor-β1 (TGF-β1), and connective tissue growth factor (CTGF). The levels of IGFBP7, TGF-β1, and CTGF were detected by enzyme linked immunosorbent assay (ELISA). Concentrations of creatinine (Cr), blood urea nitrogen (BUN), and albumin (ALB) were measured by biochemical analysis. Here, we found that LPS promoted EMT and ERK1/2 activation in HK2 cells, which were inhibited by silencing of IGFBP7. Furthermore, IGFBP7 overexpression significantly increased EMT and ERK1/2 activation in HK2 cells, which were inhibited by ERK1/2 signaling inhibitor PD98059. IGFBP7 knockdown effectively attenuated renal fibrosis, concentrations of Cr, BUN and ALB, and activation of ERK1/2 signaling in CLP-induced mice. These results suggest that inhibiting IGFBP7 can effectively protect the renal tubular epithelial cells from EMT induced by LPS or CLP both in vitro and in vivo, which may be associated with inactivation of ERK1/2 signaling.

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