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首页> 外文期刊>Cellular Signalling >Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease
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Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease

机译：PAPP-A-IGFBP-IGF-1途径在多囊肾疾病发病机制中的影响

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Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases implicated in the development of end stage renal disease (ESRD). Although FDA has recently approved a drug against ADPKD, there is still a great need for development of alternative management strategies for ADPKD. Understanding the different mechanisms that lead to cystogenesis and cyst expansion in ADPKD is imperative to develop new therapies against ADPKD. Recently, we demonstrated that caloric restriction can prevent the development of cystic disease in animal models of ADPKD and through these studies identified a new role for pregnancy associated plasma protein-A (PAPP-A), a component of the insulin-like growth factors (IGF) pathway, in the pathogenesis of this disease. The PAPP-A-IGF pathway plays an important role in regulation of cell growth, differentiation, and transformation and dysregulation of this pathway has been implicated in many diseases. Several indirect studies support the involvement of IGF-1 in the pathogenesis of ADPKD. However, it was only recently that we described a direct role for a component of this pathway in pathogenesis of ADPKD, opening a new avenue for the therapeutic approaches for this cystic disease. The present literature review will critically discuss the evidence that supports the role of components of IGF pathway in the pathogenesis of ADPKD and discuss the pharmacological implications of PAPP-A-IGF axis in this disease.
机译：常染色体占优势性多囊肾疾病（ADPKD）是最常见的遗传疾病之一，涉及开发末期肾病（ESRD）。虽然FDA最近批准了针对ADPKD的药物，但仍然有很大的需要为ADPKD制定替代管理战略。了解adpkd导致囊性发生和囊肿扩张的不同机制是对ADPKD的新疗法产生新的疗法。最近，我们证明了热量限制可以防止ADPKD动物模型中囊性疾病的发育，通过这些研究确定了妊娠相关血浆蛋白-A（PAPP-A）的新作用，胰岛素样生长因子的组分（ IGF）途径，在这种疾病的发病机制中。 PAPP-A-IGF途径在调节细胞生长，分化和转化中发挥着重要作用，并且这种途径的转化和失衡涉及许多疾病。几项间接研究支持IGF-1参与ADPKD的发病机制。然而，最近，我们描述了对ADPKD发病机制中该途径的组分的直接作用，为这种囊性疾病进行治疗方法的新途径开放了新的途径。目前的文献综述将批判性地讨论支持IGF途径组分在ADPKD发病机制中的作用的证据，并讨论这种疾病中PAPP-A-IGF轴的药理影响。

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