OVEREXPRESSION OF SNON INHIBITS HIGH-GLUCOSE–INDUCED RENAL TUBULAR EPITHELIAL MESENCHYMAL TRANSITION BY REGULATING ARKADIA EXPRESSION

Xuefeng Duan^{*, 1}, Liqiang Qin¹, Guiping He², Guangbiao Xu¹

¹Department of Nephrology, Taizhou hospital of Zhejiang Province, affiliated to Wenzhou Medical University, Taizhou 318000, Zhejiang Province, China - ²Department of Traditional Chinese Medicine, Taizhou hospital of Zhejiang Province, affiliated to Wenzhou Medical University, Taizhou 318000, Zhejiang Province, China

Objective: To explore the effect and mechanism of overexpression of nuclear transcription co-inhibitor (SnoN) on high-glucose–induced renal tubular epithelial mesenchymal transition by regulating the expression of Arkadia. 

Methods: Forty-eight 20-day-old male Sprague Dawley rats were randomly divided into control group, DM group, Sn overexpression group and over expression control group. The control group was treated with DMEM + 2% FBS containing 5.5 mmol/L glucose, and the remaining three groups were treated with DMEM + 2% FBS containing 19.5 mmol/L glucose and SnoN overexpression control vector. The protein expression levels of SnoN and EMT related proteins (CK-18, E-cadherin, α-smooth muscle actin, fibronectin, Arkadia and Smad2/3) at 2 w, 4 w and 8 w were compared.

Results: at 2 w, 4 w and 8 w, the expression of SnoN protein in renal tubular epithelial cells of the DM group was significantly lower than that of control group, and was time-dependent (P<0.05). The protein expression levels of CK-18 and E-cadherin in the DM group were significantly lower than those in the control group (P<0.05). The protein expression levels of CK-18 and E-cadherin in the SnoN overexpression group were significantly higher than those in DM group (P<0.05). The expression levels of α-SMA and FC protein in the DM group were significantly higher than those in the control group (P<0.05). The protein expression levels of α-SMA and FC in the SnoN overexpression group were significantly lower than those in the DM group (P<0.05). The protein expression levels of Arkadia and p-Smad2/3 in the DM group were significantly higher than those in the control group. The protein expression levels of Arkadia and p-Smad2/3 in the SN overexpression group were significantly lower than those in the DM group (P<0.05). 

Conclusion: The down-regulation of SnoN expression may be involved in the EMT process induced by high glucose in renal tubular epithelial cells, and its mechanism may be through the ubiquitination degradation of SnoN protein mediated by Er3 ubiquitin ligase Arkadia.