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β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2022 May 16; Vol. 23 (10). Date of Electronic Publication: 2022 May 16. - Publication Year :
- 2022
-
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.
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Animals
Cell Line
Fibrosis
Mice
Rats
Transforming Growth Factor beta metabolism
Myeloid Differentiation Factor 88 metabolism
Renal Insufficiency, Chronic metabolism
STAT3 Transcription Factor antagonists & inhibitors
STAT3 Transcription Factor metabolism
Sesquiterpenes pharmacology
Smad3 Protein antagonists & inhibitors
Smad3 Protein metabolism
Ureteral Obstruction complications
Ureteral Obstruction drug therapy
Ureteral Obstruction metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 23
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35628363
- Full Text :
- https://doi.org/10.3390/ijms23105553