Klotho-FGF23轴调控Wnt/β-catenin信号通路在CKD-MBD中的研究进展

Research Progress of Klotho-FGF23 Axis Regulating Wnt/β-catenin Sig⁃naling Pathway in CKD-MBD

肾脏疾病在当前临床背景下的发病率很高,其中慢性肾病矿物质与骨骼疾病(chronic kidney diseasemineral and bone disorder,CKD-MBD)是慢性肾脏疾病的常见并发症,发病率也比较高,会使得甲状旁腺素或钙、磷等元素出现异常代谢情况,骨代谢指标出现异常,造成血管等组织钙化问题。CKD-MBD的出现将严重影响患者的骨组织代谢,长期则会干扰远期生存质量。对此,研究CKD-MBD病理生理过程中的信号调控机制,在临床和生物学领域备受关注,也是近几年研究的热点问题之一。而过往的临床研究实践表明,Wnt/β-catenin信号通路在此病的发生中发挥很重要的作用,同时也影响肾间质纤维化的发展。这一信号通路中,Klotho-FGF23轴十分关键,负责调控该信号通路的发生、发展。Klotho-FGF23轴中,FGF23代表着成纤维细胞因子23,本质是一种蛋白质,主要在骨细胞中合成,该因子主要是参与钙、磷代谢调节工作,Klotho代表一种共受体,本质也是一种蛋白质,而且是单次跨膜蛋白质,两者结合到一起将直接作用到肾脏和甲状旁腺,因此发挥代谢调节作用。在医学研究的不断深入下,Klotho-FGF23轴调控的Wnt/β-catenin信号通路,可能会成为新时期治疗此病的新靶点。基于此,本次就立足于当前研究所得,探究上述调控过程的发展变化。

The incidence of kidney disease is very high in the current clinical background.Among them,chronic kidney disease mineral and bone disease(CKD-MBD)is a common complication of chronic kidney disease.The incidence is also relatively high,which will cause abnormal metabolism of parathyroid hormone or calcium,phosphorus and other elements,abnormal bone metabolism indicators,resulting in calcification of blood vessels and other tissues.The occurrence of CKD-MBD will seriously affect the bone metabolism of patients,and will interfere with the long-term quality of life in the long run.In this regard,the study of the signal regulation mechanism in the pathophysiological process of CKD-MBD has attracted much attention in the clinical and biological fields,and is also one of the hot issues in recent years.Previous clinical studies have shown that Wnt/β-catenin signaling pathway plays an important role in the occurrence of this disease,and also affects the development of renal interstitial fibrosis.In this signaling pathway,the Klotho-FGF23 axis is critical and is responsible for regulating the occurrence and development of this signaling pathway.In the Klotho-FGF23 axis,FGF23 represents fibroblast cytokine 23,which is essentially a protein,mainly synthesized in osteocytes.This factor is mainly involved in the regulation of calcium and phosphorus metabolism.Klotho represents a co-receptor,which is also a protein and a single transmembrane protein.The combination of the two will directly act on the kidney and parathyroid glands,thus exerting metabolic regulation.With the deepening of medical research,the Wnt/β-catenin signaling pathway regulated by the Klotho-FGF23 axis may become a new target for the treatment of this disease in the new era.Based on this,this time,based on the current research results,explore the development and changes of the above regulation process.