Emodin inhibits extracellular matrix synthesis by suppressing p38 and ERK1/2 pathways in TGF-β1-stimulated NRK-49F cells

Abstract

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.

Emodin suppresses activation of hepatic stellate cells through p38 mitogen‐activated protein kinase and Smad signaling pathways in vitro

“…Our finding of emodin‐mediated inhibition of collagen type I through suppressing p38 MAPK phosphorylation, which correlates with its activation status, in activated HSCs is consistent with the observation of B. Zhu et al () in NRK‐49F cells. These results are not unexpected because activated HSCs and NRK‐49F cells share common characteristics of ECM production and vitamin A storage.…”

“…Because MAPK is known to be noncanonical targets of TGFβ and emodin regulated p38 MAPK in NRK‐49F cells (Ding et al, ; B. Zhu et al, ), next, we tested if emodin suppresses p38 MAPK activity in activated HSCs. The data from the transcription factor activation assay presented in Figure a indicate that emodin robustiously inhibited MAPK‐induced transcription factors, including ATF‐2, signal transducer and activator of transcription 1, and myocyte enhancer factor 2 DNA binding activity in LX‐2 cells whereas DNA binding activity of c‐Jun and c‐Myc was unchanged.…”

Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages

“…In addition, rhubarb also contains several glycosides, catechins, gallic acid, and cinnamic acid, together with small amounts of tannins . Emodin and rhein exert an anti-inflammatory effect through blocking of MAPK and PI3K pathway signaling Zhu et al, 2011) and inhibition of the activation of NF-κB and iNOS expression (Li et al, 2005). For quality control and clinical use of rhubarb, it will be important to determine whether other rhubarb components exhibit anti-inflammatory activity.…”

Optimized project of traditional Chinese medicine in treating chronic kidney disease stage 3: A multicenter double-blinded randomized controlled trial

“…Previous reports have indicated that Astragalus mongholicus and salvia miltiorrhiza protect renal function in rats with acute or chronic renal failure (Huang et al, 2007;Ngai et al, 2005). Rhubarb and its derived components inhibit renal fibrosis and inflammation to repress the deterioration of renal function (Chan et al, 2003;Hu et al, 2009;Peng et al, 2005;Wang et al, 2007Wang et al, , 2009Zhu et al, 2011). Radix salviae miltiorrhizae and its derived compounds alkanic acid have renal protective effects in ischemic kidney (Shen, 1988) or ischemia/reperfusion-induced renal injury (Kang et al, 2004).…”