Tamoxifen attenuates renal fibrosis in human kidney slices and rats subjected to unilateral ureteral obstruction - 19/12/20
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| pages | 11 |
| Iconographies | 8 |
| Vidéos | 0 |
| Autres | 0 |
Graphical abstract |
Highlights |
• | Tamoxifen mitigates fibrosis in rats subjected to unilateral ureteral obstruction. |
• | Tamoxifen attenuates TGF‐β-induced fibrosis in human precision-cut tissue slices. |
• | Tamoxifen reduces fibrosis in both males and females. |
• | Tamoxifen might be used for the personalized treatment of renal injury. |
Abstract |
Background and Purpose |
Renal fibrosis plays an important role in the development and progression of chronic kidney disease (CKD). Clinical studies have shown that CKD progresses differently in males and females, which may be related to circulating levels of sex hormones. In this study, we investigated the effect of tamoxifen (TAM), a selective estrogen receptor modulator (SERM), on renal fibrosis in male and female rats subjected to unilateral ureteral obstruction (UUO) and human precision-cut kidney slices (PCKS).
Experimental Approach |
Female, ovariectomized female (OVX), and male rats were subjected to 7 days of UUO and treated with TAM by oral gavage. Moreover, we studied individual responses to TAM treatment in PCKS prepared from female and male patients. In all models, the expression of fibrosis markers was examined by western blot, qPCR, and immunohistochemistry.
Key Results |
TAM decreased the expression of fibronectin, α-smooth muscle actin, and collagen-1 and -3 in female, OVX, and male rats. In addition, TAM mitigated TGF‐β-induced fibrosis in human PCKS, irrespective of sex, yet interindividual differences in treatment response were observed.
Conclusion and Implications |
TAM ameliorates renal fibrosis in males and females, although we did observe sex differences in drug response. These findings warrant further research into the clinical applicability of TAM, or other SERMs, for the personalized treatment of renal disease.
Le texte complet de cet article est disponible en PDF.Abbreviations : CKD, ECM, ER, ESRD, FN, OVX, PCKS, SERM, TAM, UUO
Keywords : Tamoxifen, Renal fibrosis, Unilateral ureteral obstruction, Human precision-cut kidney slices
Plan
Vol 133
Article 111003- janvier 2021 Retour au numéro
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