Department of Clinical Medicine, Aarhus University, Denmark.
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, Denmark.
Biomed Pharmacother. 2021 Jan;133:111003. doi: 10.1016/j.biopha.2020.111003. Epub 2020 Nov 20.
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).
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.
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.
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.
肾纤维化在慢性肾脏病（CKD）的发生和进展中起着重要作用。临床研究表明，男性和女性的 CKD 进展方式不同，这可能与循环性激素水平有关。在这项研究中，我们研究了选择性雌激素受体调节剂（SERM）他莫昔芬（TAM）对单侧输尿管梗阻（UUO）雄性和雌性大鼠以及人精准切割肾切片（PCKS）肾纤维化的影响。
雌性、去卵巢雌性（OVX）和雄性大鼠接受 7 天 UUO 并通过口服灌胃给予 TAM 治疗。此外，我们研究了来自女性和男性患者的 PCKS 对 TAM 治疗的个体反应。在所有模型中，通过 Western blot、qPCR 和免疫组织化学检查纤维化标志物的表达。
TAM 降低了雌性、OVX 和雄性大鼠中纤维连接蛋白、α-平滑肌肌动蛋白和胶原-1 和 -3 的表达。此外，TAM 减轻了 TGF-β诱导的人 PCKS 中的纤维化，无论性别如何，但观察到治疗反应存在个体差异。
TAM 改善了雄性和雌性的肾纤维化，尽管我们确实观察到药物反应存在性别差异。这些发现值得进一步研究 TAM 或其他 SERM 用于肾脏疾病个体化治疗的临床适用性。
