title: Emodin inhibits extracellular matrix synthesis by suppressing p38 and ERK1/2 pathways in TGF-β1-stimulated NRK-49F cells.
abstract: Emodin has been demonstrated to inhibit the fibrotic process in chronic renal disease, but its mechanisms have yet to be fully elucidated. This study was carried out to investigate the effects of emodin on extracellular matrix (ECM) synthesis in TGF-β1-stimulated NRK-49F cells. NRK-49F cells stimulated with TGF-β1 were incubated with various concentrations of emodin. ECM proteins, including collagen type III and fibronectin, were detected using ELISA. ERK1/2, p38 and JNK phosphorylation were measured by Western blotting. p38, ERK1/2 and JNK were respectively inhibited with the specific inhibitors SB203580, PD98059 and SP600125. Emodin slightly inhibited the expression of fibronectin and collagen type III in NRK-49F cells without TGF-β1 treatment, and significantly suppressed fibronectin and collagen type III secretion in TGF-β1-stimulated NRK-49F cells. ERK1/2 and p38 specific inhibitors, but not JNK inhibitor, suppressed the TGF-β1-induced expression of fibronectin and collagen type III. Our previous study demonstrated that there was no crosstalk between ERK1/2, p38 and JNK signals in TGF-β1-stimulated NRK-49F cells. Here, we found that emodin inhibited the phosphorylation of ERK1/2 and p38 significantly, but did not suppress the phosphorylation of JNK. In summary, emodin suppresses fibronectin and collagen type III expression via the inhibition of ERK1/2 and p38 phosphorylation in TGF-β1-stimulated NRK-49F cells.
authors.affiliation: Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine (Hangzhou Guangxing Hospital), Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Cai-Feng
authors.initials: CF
authors.lastname: Zhu
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Zhu
authors.forename: Chen-Zhao
authors.initials: CZ
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Cheng
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D024061:Collagen Type III / Q000378:metabolism; D004642:Emodin / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005353:Fibronectins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D024061:Collagen Type III; D005353:Fibronectins; D053773:Transforming Growth Factor beta1; D007770:L-Lactate Dehydrogenase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D004642:Emodin