Strategies Targeting cAMP Signaling in the Treatment of Polycystic Kidney Disease
Strategies Targeting cAMP Signaling in the Treatment of Polycystic Kidney Disease
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DOI：
10.1681/asn.2013040398
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发表时间：
2014-01-01
影响因子：
13.6
通讯作者：
Harris, Peter C.
中科院分区：
文献类型：
--
作者：
Torres, Vicente E.;Harris, Peter C.
多囊肾病 (PKD) 是全球 ESRD 的主要原因。在 PKD 中，过度的细胞增殖和液体分泌、突变的上皮细胞与异常的细胞外基质和替代性激活的间质巨噬细胞的致病相互作用，以及控制肾小管直径的机制的破坏导致囊肿形成。动物模型研究表明，多种不同的病理生理机制（包括细胞内钙水平和 cAMP 信号传导失调）介导了这些囊肿生成机制。本文回顾了表明钙和 cAMP 在 PKD 发病机制的信号通路网络中发挥核心作用的证据，并考虑了针对 cAMP 信号传导的治疗策略的治疗相关性。
Polycystic kidney disease (PKD) is a leading cause of ESRD worldwide. In PKD, excessive cell proliferation and fluid secretion, pathogenic interactions of mutated epithelial cells with an abnormal extracellular matrix and alternatively activated interstitial macrophages, and the disruption of mechanisms controlling tubular diameter contribute to cyst formation. Studies with animal models suggest that several diverse pathophysiologic mechanisms, including dysregulation of intracellular calcium levels and cAMP signaling, mediate these cystogenic mechanisms. This article reviews the evidence implicating calcium and cAMP as central players in a network of signaling pathways underlying the pathogenesis of PKD and considers the therapeutic relevance of treatment strategies targeting cAMP signaling.