β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression.

Abstract

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.

• Authors: Wenjuan Sun, Dong Hyun Kim, Chang Hyun Byon, Hoon In Choi, Jung Sun Park, Eun Hui Bae, Seong Kwon Ma, Soo Wan Kim
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 10 (May 16 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35628363 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Myd88 protein, mouse
• Myd88 protein, rat
• Myeloid Differentiation Factor 88
• STAT3 Transcription Factor
• Sesquiterpenes
• Smad3 Protein
• Smad3 protein, mouse
• Smad3 protein, rat
• Stat3 protein, mouse
• Stat3 protein, rat
• Transforming Growth Factor beta
• beta-elemene

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Cell Line
• Fibrosis
• Mice
• Myeloid Differentiation Factor 88 (metabolism)
• Rats
• Renal Insufficiency, Chronic (metabolism)
• STAT3 Transcription Factor (antagonists & inhibitors, metabolism)
• Sesquiterpenes (pharmacology)
• Smad3 Protein (antagonists & inhibitors, metabolism)
• Transforming Growth Factor beta (metabolism)
• Ureteral Obstruction (complications, drug therapy, metabolism)