Moor Matthias B, Bonny Olivier
Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
The National Centre of Competence in Research (NCCR) "Kidney.CH - Kidney Control of Homeostasis" Switzerland, Zürich, Switzerland.
Physiol Rep. 2020 Apr;8(7):e14410. doi: 10.14814/phy2.14410.
Mediator of cell motility 1 (MEMO1) is a ubiquitously expressed modulator of cellular responses to growth factors including FGF23 signaling, and Memo1-deficient mice share some phenotypic traits with Fgf23- or Klotho-deficient mouse models. Here, we tested whether Memo1 gene expression is regulated by calciotropic hormones or by changing the dietary mineral load. MLO-Y4 osteocyte-like cells were cultured and treated with 1,25(OH) -vitamin D . Wild-type C57BL/6N mice underwent treatments with 1,25(OH) -vitamin D , parathyroid hormone, 17β-estradiol or vehicle. Other cohorts of C57BL/6N mice were fed diets varying in calcium or phosphate content. Expression of Memo1 and control genes was assessed by qPCR. 1,25(OH) -vitamin D caused an acute decrease in Memo1 transcript levels in vitro, but not in vivo. None of the hormones tested had an influence on Memo1 transcripts, whereas the assessed control genes reacted the expected way. Dietary interventions with calcium and phosphate did not affect Memo1 transcripts but altered the chosen control genes' expression. We observed that Memo1 was not regulated by calciotropic hormones or change in mineral load, suggesting major differences between the regulation and physiological roles of Klotho, Fgf23, and Memo1.
细胞运动介质1(MEMO1)是一种在细胞中普遍表达的调节因子,可调节细胞对包括FGF23信号在内的生长因子的反应,并且缺乏Memo1基因的小鼠与缺乏Fgf23或Klotho基因的小鼠模型具有一些共同的表型特征。在此,我们测试了Memo1基因表达是否受钙调节激素或饮食矿物质负荷变化的影响。培养MLO-Y4骨细胞样细胞并用1,25(OH)₂-维生素D进行处理。野生型C57BL/6N小鼠接受1,25(OH)₂-维生素D、甲状旁腺激素、17β-雌二醇或赋形剂处理。其他C57BL/6N小鼠群体被喂食钙或磷含量不同的饮食。通过qPCR评估Memo1和对照基因的表达。1,25(OH)₂-维生素D在体外导致Memo1转录水平急剧下降,但在体内未出现这种情况。所测试的激素均未对Memo1转录本产生影响,而所评估的对照基因则呈现出预期的反应。钙和磷的饮食干预未影响Memo1转录本,但改变了所选对照基因的表达。我们观察到Memo1不受钙调节激素或矿物质负荷变化的调节,这表明Klotho、Fgf23和Memo1在调节和生理作用方面存在重大差异。