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

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Tamoxifen attenuates renal fibrosis in human kidney slices and rats subjected to unilateral ureteral obstruction. / Tingskov, Stine Julie; Jensen, Michael Schou; Pedersen, Casper Emil Tingskov et al.

I: Biomedicine and Pharmacotherapy, Bind 133, 111003, 01.2021.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{3725384acd134021a50234472feecece,
title = "Tamoxifen attenuates renal fibrosis in human kidney slices and rats subjected to unilateral ureteral obstruction",
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.",
keywords = "Human precision-cut kidney slices, Renal fibrosis, Tamoxifen, Unilateral ureteral obstruction",
author = "Tingskov, {Stine Julie} and Jensen, {Michael Schou} and Pedersen, {Casper Emil Tingskov} and {de Araujo}, {Isabela Bastos Binotti Abreu} and Mutsaers, {Henricus A.M.} and Rikke N{\o}rregaard",
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.]. Publisher Copyright: {\textcopyright} 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2021",
month = jan,
doi = "10.1016/j.biopha.2020.111003",
language = "English",
volume = "133",
journal = "Biomedicine & Pharmacotherapy",
issn = "0753-3322",
publisher = "Elsevier Masson",

}

RIS

TY - JOUR

T1 - Tamoxifen attenuates renal fibrosis in human kidney slices and rats subjected to unilateral ureteral obstruction

AU - Tingskov, Stine Julie

AU - Jensen, Michael Schou

AU - Pedersen, Casper Emil Tingskov

AU - de Araujo, Isabela Bastos Binotti Abreu

AU - Mutsaers, Henricus A.M.

AU - Nørregaard, Rikke

N1 - 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.]. Publisher Copyright: © 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

KW - Human precision-cut kidney slices

KW - Renal fibrosis

KW - Tamoxifen

KW - Unilateral ureteral obstruction

UR - http://www.scopus.com/inward/record.url?scp=85096443214&partnerID=8YFLogxK

U2 - 10.1016/j.biopha.2020.111003

DO - 10.1016/j.biopha.2020.111003

M3 - Journal article

C2 - 33227702

AN - SCOPUS:85096443214

VL - 133

JO - Biomedicine & Pharmacotherapy

JF - Biomedicine & Pharmacotherapy

SN - 0753-3322

M1 - 111003

ER -