Regulation of intracellular decorin via proteasome degradation in rat mesangial cells.
Decorin (DCN) is a member of small leucine-rich proteoglycan family that neutralizes the bioactivity of transforming growth factor-beta1 (TGF-β1). It has been proven to be a promising anti-fibrotic agent to treat glomerulonephritis. But the underlining mechanism for regulating and degrading intracellular DCN is still not fully understood. In this study, we investigated the roles of ubiquitination in the regulation of cytoplasmic DCN metabolism in rat mesangial cells (MC) by immunoprecipitation and Western blot. The results showed that a proportion of cytoplasmic DCN was ubiquitinated in normal MC and was enhanced in N-glycosylation inhibitor (tunicamycin)-treated MC. After being treated with the proteasome inhibitor MG132, ubiquitinated DCN accumulated and displayed a prolonged half-life, accompanied by decreased TGF-β1 expression and reduced collagen IV mRNA level in MC. This study demonstrated that the stability and function of cytoplasmic DCN can be regulated by ubiquitin-proteasome system (UPS) in MC, which implies that regulating the ubiquitination and degradation of DCN might be a novel approach for modulating MC bioactivity.
Wu
Huijuan
H
Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China.
Jiang
Weina
W
Zhang
Yan
Y
Liu
Ye
Y
Zhao
Zhonghua
Z
Guo
Muyi
M
Ma
Duan
D
Zhang
Zhigang
Z
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D058575:Decorin / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006031:Glycosylation; D006207:Half-Life; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D054875:Ubiquitination / Q000187:drug effects
D024141:Collagen Type IV; D058575:Decorin; D007976:Leupeptins; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014415:Tunicamycin; D003513:Cycloheximide; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde