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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; de Araujo, Isabela Bastos Binotti Abreu; Mutsaers, Henricus A M; Nørregaard, Rikke.
Afiliación
  • Tingskov SJ; Department of Clinical Medicine, Aarhus University, Denmark.
  • Jensen MS; Department of Clinical Medicine, Aarhus University, Denmark.
  • Pedersen CT; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, Denmark.
  • de Araujo IBBA; Department of Clinical Medicine, Aarhus University, Denmark.
  • Mutsaers HAM; Department of Clinical Medicine, Aarhus University, Denmark.
  • Nørregaard R; Department of Clinical Medicine, Aarhus University, Denmark. Electronic address: rn@clin.au.dk.
Biomed Pharmacother ; 133: 111003, 2021 Jan.
Article en En | MEDLINE | ID: mdl-33227702
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-ß-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tamoxifeno / Obstrucción Ureteral / Moduladores Selectivos de los Receptores de Estrógeno / Riñón / Enfermedades Renales Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Biomed Pharmacother Año: 2021 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Francia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tamoxifeno / Obstrucción Ureteral / Moduladores Selectivos de los Receptores de Estrógeno / Riñón / Enfermedades Renales Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Biomed Pharmacother Año: 2021 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Francia