Honokiol ameliorates renal fibrosis by inhibiting extracellular matrix and pro-inflammatory factors in vivo and in vitro
| Autor: | Cheng-Tien Wu, Chih-Kang Chiang, Chin-Ching Yang, Shing-Hwa Liu, Yi Wei Lin, Meei-Ling Sheu, Min-Wei Chen, Kuan-Dun Wu, Kuan-Yu Hung |
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| Rok vydání: | 2011 |
| Předmět: |
Pharmacology
Honokiol medicine.medical_specialty biology business.industry urologic and male genital diseases medicine.disease Fibronectin CTGF chemistry.chemical_compound Endocrinology chemistry In vivo Fibrosis Internal medicine Tubulointerstitial fibrosis medicine Renal fibrosis biology.protein Cancer research Epithelial–mesenchymal transition business |
| Zdroj: | British Journal of Pharmacology. 163:586-597 |
| ISSN: | 0007-1188 |
| DOI: | 10.1111/j.1476-5381.2011.01242.x |
| Popis: | BACKGROUND AND PURPOSE Renal fibrosis acts as the common pathway leading to the development of end-stage renal disease. The present study investigated, in vivo and in vitro, the anti-fibrotic and anti-inflammatory effects, particularly on the epithelial to mesenchymal transition of renal tubular cells, exerted by honokiol, a phytochemical used in traditional medicine, and mechanisms underlying these effects. EXPERIMENTAL APPROACH Anti-fibrotic effects in vivo were assayed in a rat model of renal fibrosis [the unilateral ureteral obstruction (UUO) model]. A rat tubular epithelial cell line (NRK-52E) was stimulated by transforming growth factor-β1 (TGF-β1) and treated with honokiol to explore possible mechanisms of these anti-fibrotic effects. Gene or protein expression was analysed by Northern or Western blotting. Transcriptional regulation was investigated using luciferase activity driven by a connective tissue growth factor (CTGF) promoter. KEY RESULTS Honokiol slowed development of renal fibrosis both in vivo and in vitro. Honokiol treatment attenuated tubulointerstitial fibrosis and expression of pro-fibrotic factors in the UUO model. Honokiol also decreased expression of the mRNA for the chemokine CCL2 and for the intracellular adhesion molecule-1, as well as accumulation of type I (α1) collagen and fibronectin in UUO kidneys. Phosphorylation of Smad-2/3 induced by TGF-β1 and CTGF luciferase activity in renal tubular cells were also inhibited by honokiol. CONCLUSIONS AND IMPLICATIONS Honokiol suppressed expression of pro-fibrotic and pro-inflammatory factors and of extracellular matrix proteins. Honokiol may become a therapeutic agent to prevent renal fibrosis. |
| Databáze: | OpenAIRE |
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