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Ubiquitin-dependent Degradation of SnoN/Ski Protein in Glomerular Mesangial Cells Induced by High Glucose

Author: NanQingLing
Tutor: XuYong
School: Luzhou Medical College
Course: Internal Medicine
Keywords: SnoN / Ski Ubiquitin - proteasome pathway Arkadia Diabetic nephropathy
CLC: R587.2
Type: Master's thesis
Year: 2011
Downloads: 53
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Abstract

Purpose: TGF-β Diabetic Nephropathy (Diabetic Nephropathy, DN) of a variety of pathogenic factors the intersection can induce kidney inherent cell phenotypic and promote extracellular matrix (extracellular matrix, ECM) accumulate in renal fibrosis play an important role in sexual development. SnoN / Ski transforming growth factor -β/Smad (tansforming growth factor-β/Smad important negative regulatory factor of TGF-β/Smad) signaling pathway, they can interact with Smad proteins, inhibition of TGF-p target gene activation, regulation of the biological effects of TGF-β. Recent studies have found that the nuclear transcription corepressor SnoN / Ski mainly through the ubiquitin - proteasome pathway (Ubiquitin-Proteasome Pathway, UPP) degradation. The relevant diabetic nephropathy there are few studies of the ubiquitin-proteasome pathway. Diabetes, the kidneys of the ubiquitin-proteasome pathway activation, cell signaling protein ubiquitination is enhanced, not been reported. Previous studies found that fiber nephropathy induced in mice with unilateral ureteral obstruction after surgery (UUO) model, SnoN / Ski mRNA expression increased SnoN / Ski protein expression decreased significantly reduced SnoN / Ski proteins is mainly due to the E3 ubiquitin ligase-mediated ubiquitination and degradation due to the increase. Therefore, the present study was to investigate the role of high-sugar rat mesangial cells (GMC) SnoN / Ski ubiquitin connections enzyme Arkadia protein expression changes, and as an intervention with the proteasome inhibitor MG132 factors discussed SnoN / Ski ubiquitination degradation in the DN. Methods: cultured rat GMC (HBZY-1) were divided into five groups with a high sugar as a stimulating factor, MG132 ubiquitin proteasome inhibitor, are located: (1) normal control group: the medium containing 5.6mmol / L glucose; ② high sugar Group A: culture medium containing 20mmol / L glucose; ③ high sugar Pool B: medium containing 30mmol / L glucose; ④ mannitol group: medium containing 5.6mmol / L glucose 24.4 mmol / L mannitol, as high sugar B of osmotic pressure control; ⑤ high sugar MG132 group: 30mmol / L glucose medium pretreated with 0.5umol / L-specific ubiquitin proteasome inhibitor MG132. Cells after 48h, using a Western blot (western-blot) and immunofluorescence staining laser confocal microscope to detect the expression SnoN the Ski and Arkadia protein expression. Results: 1, normal mesangial cells SnoN / Ski protein expression of high glucose SnoN / Ski protein expression was decreased, and with the increase of glucose concentration and prolonged duration of action, SnoN / Ski protein weakened more obvious in a time , concentration-dependent, statistically significant difference (P lt; 0.01). With high glucose group, the high sugar MG132 group SnoN / Ski protein expression increased, and the difference was statistically significant (P lt; 0.01). Comparison with the normal group, no significant change in mannitol group (P gt; 0.05). 2 Arkadia protein expression in normal mesangial cells is weak. Compared with the normal control group, high glucose after 48h, Arkadia protein increases, the difference was statistically significant (P lt; 0.01). Compared with the high-sugar group, high sugar MG132 Arkadia protein expression decreased, and the difference was statistically significant (P lt; 0.01). Mannitol group and the normal group Arkadia protein expression was no significant difference (P gt; 0.05). Conclusion: 1, high-sugar by the ubiquitin-proteasome pathway degradation of SnoN / Ski proteins caused by its low expression. E3 ligase the Arkadia involved in the high glucose-induced SnoN / Ski ubiquitination and degradation.

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