β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression.
Wenjuan SunDong-Hyun KimChang Hyun ByonHoon In ChoiJung Sun ParkEun Hui BaeSeong Kwon MaYong-Soo KimPublished in: International journal of molecular sciences (2022)
Renal fibrosis is a chronic pathological process that seriously endangers human health. However, the current therapeutic options for this disease are extremely limited. Previous studies have shown that signaling factors such as JAK2/STAT3, Smad3, and Myd88 play a regulatory role in renal fibrosis, and β-elemene is a plant-derived sesquiterpenoid organic compound that has been shown to have anti-inflammatory, anti-cancer, and immunomodulatory effects. In the present study, the anti-fibrotic effect of β-elemene was demonstrated by in vivo and in vitro experiments. It was shown that β-elemene inhibited the synthesis of extracellular matrix-related proteins in unilateral ureteral obstruction mice, and TGF-β stimulated rat interstitial fibroblast cells, including α-smooth muscle actin, vimentin, and connective tissue growth factor, etc. Further experiments showed that β-elemene reduced the expression levels of the above-mentioned fibrosis-related proteins by blocking the phosphorylation of JAK2/STAT3, Smad3, and the expression or up-regulation of MyD88. Notably, knockdown of MyD88 attenuated the phosphorylation levels of STAT3 and Smad3 in TGF-β stimulated NRK49F cell, which may be a novel molecular mechanism by which β-elemene affects renal interstitial fibrosis. In conclusion, this study elucidated the anti-interstitial fibrosis effect of β-elemene, which provides a new direction for future research and development of drugs related to chronic kidney disease.
Keyphrases
- transforming growth factor
- growth factor
- poor prognosis
- epithelial mesenchymal transition
- extracellular matrix
- chronic kidney disease
- smooth muscle
- human health
- toll like receptor
- risk assessment
- liver fibrosis
- anti inflammatory
- induced apoptosis
- cell proliferation
- stem cells
- oxidative stress
- binding protein
- immune response
- signaling pathway
- skeletal muscle
- type diabetes
- long non coding rna
- inflammatory response
- adipose tissue
- metabolic syndrome
- mesenchymal stem cells
- insulin resistance
- cell death
- end stage renal disease
- cell therapy
- high fat diet induced
- case control