| First Author | Ko YM | Year | 2013 |
| Journal | Arch Biochem Biophys | Volume | 535 |
| Issue | 2 | Pages | 177-86 |
| PubMed ID | 23500140 | Mgi Jnum | J:206701 |
| Mgi Id | MGI:5551703 | Doi | 10.1016/j.abb.2013.03.003 |
| Citation | Ko YM, et al. (2013) Ubiquitin C-terminal hydrolase-L5 is required for high glucose-induced transforming growth factor-beta receptor I expression and hypertrophy in mesangial cells. Arch Biochem Biophys 535(2):177-86 |
| abstractText | Transforming growth factor-beta (TGF-beta) is pivotal in the pathogenesis of diabetic nephropathy. Type 1 TGF-beta receptor (TGF-betaR1) 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 (27.8mM)-induced TGF-betaR1 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-betaR1 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-betaR1 protein expression and TGF-betaR1 protein deubiquitination were attenuated by UCHL5 shRNA. Additionally, high glucose-induced p21(WAF1), fibronectin protein expression and cell hypertrophy were attenuated by UCHL5 shRNA. However, high glucose-induced TGF-betaR1 mRNA, p27(kip1) protein expression and growth inhibition were not affected by UCHL5 shRNA. Finally, glomerular UCHL5 and TGF-betaR1 protein expression were increased in streptozotocin-diabetic rats at 8weeks. We conclude that PI3K-dependent UCHL5 is required for high glucose-induced TGF-betaR1 protein expression in mesangial cells. UCHL5 is also required for high glucose-induced TGF-betaR1 protein deubiquitination, p21(WAF1) and fibronectin protein expression and cell hypertrophy. |
