自噬与ADPKD

Autophagy and Autosomal Dominant Polycystic Kidney Disease

摘要: 自噬是胞质内成分被转运至溶酶体内降解为初级成分的过程，以维持细胞内稳态和能量产生，其三条通路包括巨自噬、分子伴侣介导的自噬和微自噬。自噬参与到某些肾脏疾病的病理过程中，如急性肾损伤、糖尿病肾病和常染色体显性遗传多囊肾病(autosomal dominant polycystic kidney disease, ADPKD)。ADPKD由Pkd1或Pkd2基因的突变引起，致使细胞内钙离子稳态失衡，进而导致肾囊泡的形成及生长。一些涉及囊泡生长的信号通路也参与自噬的调节，因此PKD的病理机制与自噬存在密切联系。本文主要对PKD与自噬的调节以及自噬与凋亡、mTOR信号通路及纤毛功能之间的关系等方面的研究进展进行综述。

Abstract: Autophagy is the process that cytoplasmic components are transported into lysosomes and de-graded to primary components, maintaining the cellular homeostasis and energy production. The three pathways of autophagy include macroautophagy, chaperone-mediated autophagy, and microautophagy. Autophagy is involved in pathogenesis of several important renal diseases, such as acute kidney injury, diabetic nephropathy and autosomal dominant polycystic kidney disease (ADPKD). ADPKD is caused by mutations of Pkd1 or Pkd2, resulting in the imbalance of intracellular calcium and furthermore the formation and growth of cysts. Several pathways involved in cyst growth also play a role in autophagy, thus implying the association of pathogenesis of PKD and autophagy. Overall, we reviewed the suppressed autophagy in PKD, and the relation between autophagy and apoptosis, mTOR signaling pathway, and ciliary function in PKD.