Abstract:

Objective    To explore whether emodin ameliorates high-glucose-induced mesangial cell hypo-contractility by inhibiting p38MAPK over-activation.  Methods    Mesangial cells were divided into five groups： the normal glucose group (5.6mmol/L glucose, NG group), the high glucose group (30mmol/L glucose, HG group), the low-dose emodin group (50mg/L emodin+ 30mmol/L glucose， LE group), the high-dose emodin group (100mg/L emodin+30mmol/L glucose, HE group), and the GW9662 group (10μmol/L GW9662+ 30mmol/L glucose+100mg/L emodin, GW group). Angiotensin Ⅱ-stimulated cell surface reduction was measured to evaluate cell contractility. p38MAPK activity and PPARγ expression were detected by using Western blot and real-time polymerase chain reaction(Real-time PCR).  Results    High-glucose resulted in an increase   in p38MAPK activity and significant impairment of mesangial contractility（P<0.05）; emodin treatment dose-dependently inhibited high-glucose-induced p38MAPK overactivation(a 40% decrease for 50mg/L emodin and a 73% decrease for 100 mg/L emodin), and mesangial hypo-contractility was ameliorated by emodin（P<0.05）; both the PPARγ mRNA and protein levels were elevated after emodin treatment（P<0.05）;  inhibition of PPARγ using GW9662 effectively blocked ameliorating effects of emodin on high-glucose-induced p38MAPK over-activation and mesangial hypo-contractility（P<0.05）. Conclusion     Emodin effectively ameliorates high-glucose-induced p38MAPK over- activation via activation of PPARγ, and therefore, ameliorateshypo-contractility of mesangial cells.

Key words: Emodin; High glucose; Mesangial cells; p38 mitogen-activated protein kinases; Peroxisome proliferator activated receptors gamma