SnoN as a key regulator of the high glucose-induced epithelial-mesenchymal transition in cells of the proximal tubule.
OBJECTIVE
Ski-related protein N (SnoN) suppression is essential to transforming growth factor-β1 induction and the epithelial-mesenchymal transition (EMT) in several cancer cells. The role of SnoN in diabetic nephropathy is unknown. We aimed to determine the role of SnoN in the EMT of proximal tubule cells (PTCs) maintained under high glucose conditions.


METHODS
Immunohistochemistry, immunocytochemistry, Western blotting, small interfering RNA gene silencing, viral transduction and RT-PCR were used to assess changes in SnoN, E-cadherin, cytokeratin-18, α-smooth muscle actin and fibronectin expression using an in vivo streptozotocin-induced rat diabetic nephropathy model, and PTCs exposed to high glucose (25 mmol/l).


RESULTS
High glucose induced EMT in vitro and in vivo. Exposure of PTCs to a high concentration of glucose suppressed SnoN expression in a time-dependent manner compared with normal glucose and high osmolarity-treated groups. SnoN gene silencing under high glucose conditions appears to enhance the transition of PTC phenotype. Conversely, ectopic expression of exogenous SnoN after transfection conferred tubular epithelial cell resistance to high glucose-induced EMT.


CONCLUSIONS
SnoN plays a negative role in high glucose-induced EMT in PTCs. The effect of SnoN downregulation in vivo and in vitro suggests that SnoN may be a potential therapeutic target.
Department of Pathophysiology, Guiyang Medical University, Guiyang, China.
Ruixia
R
Liu
Yuanyuan
Y
Wang
Ying
Y
Xiao
Mingjun
M
Shi
Guozhong
G
Zhang
Bing
B
Guo
D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage* / Q000633:toxicity; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000502:physiology*
D009419:Nerve Tissue Proteins; C511209:Skil_v1 protein, rat; D014157:Transcription Factors; D005947:Glucose