Emodin ameliorates high-glucose induced mesangial p38 over-activation and hypocontractility via activation of PPARgamma.
Early stage diabetic nephropathy is characterized by elevated glomerular filtration. Recent studies have identified high-glucose induced p38 MAPK (p38) over-activation in mesangial cells. Mesangial hypocontractility is the major underlying mechanism, however, no ameliorating agents are currently available. We investigated the protective effects of emodin on high-glucose induced mesangial cell hypocontractility. Mesangial cells were cultured under normal (5.6 mM) and high glucose (30 mM) conditions. Emodin was administrated at doses of 50 mg/l and 100 mg/l. Angiotension II stimulated cell surface reductions were measured to evaluate cell contractility. p38 activity was detected using Western blotting. To further explore the possible mechanism of emodin, expression of the peroxisome proliferator- activated receptorgamma (PPARgamma) was measured and its specific inhibitor, gw9662, was administrated. Our results showed: (1) high-glucose resulted in a 280% increase in p38 activity associated with significant impairment of mesangial contractility; (2) emodin treatment dose-dependently inhibited high-glucose induced p38 over-activation (a 40% decrease for 50 mg/l emodin and a 73% decrease for 100 mg/l emodin), and mesangial hypocontractility was ameriolated by emodin; (3) both the PPARgamma mRNA and protein levels were elevated after emodin treatment; (4) inhibition of PPARgamma using gw9662 effectively blocked the ameliorating effects of emodin on high-glucose induced p38 over-activation and mesangial hypocontractility. Emodin effectively ameliorated p38 over-activation and hypocontractility in high-glucose induced mesangial cells, possibly via activation of PPARgamma.
Liu
Yi
Y
Department of Nephrology, Shandong Provincial Hospital, Shandong University, Shandong 250021, China.
Jia
Lei
L
Liu
Zun Chang
ZC
Zhang
Hong
H
Zhang
Peng Ju
PJ
Wan
Qiang
Q
Wang
Rong
R
D000818:Animals; D002460:Cell Line; D002468:Cell Physiological Phenomena / Q000187:drug effects; D004642:Emodin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D004642:Emodin