Title of article :
Ubiquitin C-terminal hydrolase-L5 is required for high glucose-induced transforming growth factor-β receptor I expression and hypertrophy in mesangial cells
Author/Authors :
Ko، نويسنده , , Yu-Min and Chang، نويسنده , , Chun-Ying and Chiou، نويسنده , , Shean-Jaw and Hsu، نويسنده , , Fu-Jie and Huang، نويسنده , , Jau-Shyang and Yang، نويسنده , , Yu-Lin and Guh، نويسنده , , Jinn-Yuh and Chuang، نويسنده , , Lea-Yea، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2013
Pages :
10
From page :
177
To page :
186
Abstract :
Transforming growth factor-β (TGF-β) is pivotal in the pathogenesis of diabetic nephropathy. Type 1 TGF-β receptor (TGF-βR1) is degraded by Smad7-dependent ubiquitination–proteasomal pathway, which is deubiquitinated by ubiquitin C-terminal hydrolase-L5 (UCHL5). Therefore, we studied the role of UCHL5 in high glucose (27.8 mM)-induced TGF-βR1 protein expression in mouse mesangial (MES13) cells. UCHL5 short hairpin RNA (shRNA) was used to knock down UCHL5 while LY294002 and the dominant-negative p85 were used to inhibit phosphatidylinositol-3-kinase (PI3K). We found that high glucose increased phospho-Akt, TGF-βR1 mRNA and protein expression. High glucose also increased UCHL5 protein expression, which was attenuated by LY294002, the dominant-negative p85 and the dominant-negative CREB. High glucose-induced TGF-βR1 protein expression and TGF-βR1 protein deubiquitination were attenuated by UCHL5 shRNA. Additionally, high glucose-induced p21WAF1, fibronectin protein expression and cell hypertrophy were attenuated by UCHL5 shRNA. However, high glucose-induced TGF-βR1 mRNA, p27kip1 protein expression and growth inhibition were not affected by UCHL5 shRNA. Finally, glomerular UCHL5 and TGF-βR1 protein expression were increased in streptozotocin-diabetic rats at 8 weeks. We conclude that PI3K-dependent UCHL5 is required for high glucose-induced TGF-βR1 protein expression in mesangial cells. UCHL5 is also required for high glucose-induced TGF-βR1 protein deubiquitination, p21WAF1 and fibronectin protein expression and cell hypertrophy.
Keywords :
ubiquitination , High glucose , Mesangial cells , TGF-? , UCHL5
Journal title :
Archives of Biochemistry and Biophysics
Serial Year :
2013
Journal title :
Archives of Biochemistry and Biophysics
Record number :
1633508
Link To Document :
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