Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive renal cyst formation and expansion. Several clinical trials show that somatostatin analogs halt cyst growth and progression of ADPKD by inhibiting adenosine 3′,5′-cyclic monophosphate (cAMP) signaling. However, two studies suggest that the effect of the somatostatin analog octreotide on kidney growth during the first year of treatment is reduced in the subsequent follow-ups and the kidney enlargement resumes. We hypothesize that this biphasic change in kidney growth during octreotide treatment may be due to changes in somatostatin receptor 2 (SSTR2) expression. Here we analyzed the expression of renal SSTR2 in various polycystic kidney disease (PKD) mouse models in which PKD1 gene expression was disrupted on postnatal day 10 or 18 by tamoxifen. Using immunohistochemical analysis, we showed that the distribution of SSTR2 in murine kidneys is mainly in distal tubules and collecting ducts. In addition, in both PKD models, we observed a significant decrease in SSTR2 expression in epithelia of dilated tubules and cystic epithelia in mice with end stage of PKD compared to wild-type mice. These findings were further confirmed by quantitative PCR (qPCR) on mRNA levels of SSTR2. In conclusion, our data show that SSTR2 expression levels are reduced during kidney cyst growth, which may suggest reduced efficacy in long-term treatment with somatostatin analogs.
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