Tamoxifen attenuates renal fibrosis in human kidney slices and rats subjected to unilateral ureteral obstruction

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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.

TidsskriftBiomedicine and Pharmacotherapy
StatusUdgivet - jan. 2021

Bibliografisk note

Funding Information:
This study was supported by the Danish Council for Independent Research Medical Sciences [grant number 6110-00231B ], the Aarhus University Research Foundation [grant number AUFF-E-2015-FLS-8-69 ], the Hildur and Dagny Jacobsens Foundation [grant number 1295716-1] , received by R.N., the Lundbeck foundation [grant number R231-2016-2344 , received by H.A.M.M.], and the Aase og Ejnar Danielsens Fond [grant number 19-10-0408 , received by S.J.T.].

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© 2020 The Authors

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