1 Department of Human Genetics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
2 Department of Pathology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
Exp Biol Med (Maywood). 2018 Sep;243(13):1092-1098. doi: 10.1177/1535370218803893. Epub 2018 Sep 27.
Somatostatin (SST) analogs have been shown to halt cyst growth and progression of autosomal dominant polycystic kidney disease by several clinical trials. However, two studies suggest that the effect of the SST analog octreotide on kidney growth during the first year of treatment is reduced in the subsequent follow-ups and the kidney enlargement resumes. This biphasic change in kidney growth during octreotide treatment may be partially explained by alterations in SSTR2 expression. Here, we found that SSTR2 is mainly expressed in distal tubules and collecting ducts in murine kidneys, and the expression of SSTR2 decreases during cyst growth in two PKD mouse models. Our data may thus provide possible explanations for the lack of efficacy in long-term treatment with SST analogs.
生长抑素(SST)类似物已被多项临床试验证明可阻止常染色体显性多囊肾病的囊肿生长和进展。然而,有两项研究表明,SST 类似物奥曲肽在治疗的第一年对肾脏生长的作用在随后的随访中减弱,肾脏增大恢复。奥曲肽治疗期间肾脏生长的这种双相变化可能部分归因于 SSTR2 表达的改变。在这里,我们发现 SSTR2 主要在小鼠肾脏的远曲小管和集合管中表达,并且在两种 PKD 小鼠模型中囊肿生长期间 SSTR2 的表达减少。因此,我们的数据可能为 SST 类似物长期治疗缺乏疗效提供了可能的解释。