The role of PPARα in autosomal dominant polycystic kidney disease.
The role of PPARα in autosomal dominant polycystic kidney disease.
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PPARα在常染色体显性多囊肾病中的作用。
DOI：
10.1097/mnh.0000000000000615
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发表时间：
2020-07
影响因子：
3.2
通讯作者：
Lakhia R
中科院分区：
文献类型：
--
作者：
Lakhia R
代谢重编程是常染色体显性遗传性多囊肾病囊肿上皮细胞的显著特征。过氧化物酶体增殖物激活受体α（Peroxisome Proliferator Activated Receptor alpha，Pparα）是一种调节细胞代谢的转录因子。本文就Pparα在ADPKD中的作用作一综述。Pparα表达在小鼠和人的ADPKD肾脏中降低。这种下调部分继发于microRNA介导的翻译抑制，并导致脂肪酸代谢受损。遗传学研究表明，在ADPKD的缓慢进展的小鼠模型中，Pparα的缺失可促进囊肿生长。最近的研究还表明，给予Pparα激动剂可改善小鼠的囊肿负荷。Pparα的异常降低影响ADPKD的细胞代谢。Pparα是ADPKD小鼠模型中囊肿进展的调节剂。这些研究确定Pparα是治疗ADPKD患者的令人兴奋的新药靶点。
Metabolic reprogramming is a prominent feature of cyst epithelial cells in autosomal dominant polycystic kidney disease. Peroxisome proliferator activated receptor alpha (Pparα) is a transcription factor that regulates many aspects of cellular metabolism. The purpose of this review is to understand the role of Pparα in ADPKD. Pparα expression is reduced in ADPKD kidneys of mice and humans. This downregulation is in part secondary to microRNA mediated translational repression and leads to impairment of fatty acid metabolism. Genetic studies demonstrate that deletion of Pparα aggravates cyst growth in a slowly progressive mouse model of ADPKD. Recent studies also show that administration of Pparα agonists ameliorates cyst burden in mice. Abnormal reduction of Pparα affects cellular metabolism in ADPKD. Pparα is a modulator of cyst progression in mouse models of ADPKD. These studies establish Pparα as an exciting new drug target for the treatment of individuals with ADPKD.