Emodin suppresses interleukin-1beta induced mesangial cells proliferation and extracellular matrix production via inhibiting P38 MAPK.
Previous findings indicate that emodin has anti-proliferation and anti-fibrosis effects on several cell lines. In this study, we investigated the effects of emodin on IL-1beta induced proliferation of mesangial cells (MCs) and on their production of extracellular matrix (ECM), and explored the possible mechanisms. To test the therapeutic effect of emodin on progressive renal disease, we administered emodin to rats in renal failure models induced by subtotal nephrectomy, the renal function was analyzed. Our results showed emodin significantly suppressed IL-1beta induced MC proliferation and arrested the cell-cycle progress in vitro. Fibronectin and collagen IV production by MC were significantly reduced after emodin treatment. P38 mRNA, protein levels of P-P38, P-MKK3/6 and P-MKK4 were quantified. We observed no alterations of P38 expression and P-MKK4 protein content; however, protein levels of P-P38 and P-MKK3/6 significantly decreased after emodin treatment. In the renal failure models, after administration of emodin for eight weeks, the rat renal lesions were significantly ameliorated, as evidenced by the decreased blood creatinine, urea, and the 24-hour urine protein. In conclusion, emodin suppresses IL-1beta induced MC proliferation and ECM production in vitro. We hypothesize that this is achieved by inactivating MKK3/6 and P38. Emodin ameliorates renal failure in subtotal nephrectomized rats, which suggests a potential role of emodin in the treatment of progressive renal diseases.
Wang
Rong
R
Department of Nephrology, Shandong Provincial Hospital Shandong University, Jinan, Shandong, China. wangrong2@medmail.com.cn
Wan
Qiang
Q
Zhang
Ying
Y
Huang
Fangfang
F
Yu
Kezhou
K
Xu
Dongmei
D
Wang
Qun
Q
Sun
Jing
J
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D004642:Emodin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000187:drug effects*; D005434:Flow Cytometry; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D013778:Tetrazolium Salts; D013844:Thiazoles; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
D053583:Interleukin-1beta; D013778:Tetrazolium Salts; D013844:Thiazoles; D048051:p38 Mitogen-Activated Protein Kinases; C022616:thiazolyl blue; D004642:Emodin