Soluble receptor for advanced glycation end products inhibits disease progression in autosomal dominant polycystic kidney disease by down-regulating cell proliferation.

Autosomal polycystic kidney disease (ADPKD) is a highly prevalent genetic renal disorder in which epithelial-lining fluid-filled cysts appear in kidneys. It is accompanied by hyperactivation of cell proliferation, interstitial inflammation, and fibrosis around the cyst lining cells, finally reaching end-stage renal disease. Previously, we found high expression of ligands stimulating the receptor for advanced glycation end products in ADPKD mice. Furthermore, gene silencing of was revealed to cause reduction of cystogenesis via down-regulation of cell proliferation in vitro, and intravenous administration of adenovirus in vivo also displayed alleviation of the disease. Here, we attempted to identify the role of soluble duanyu1648 in inhibiting the progression of ADPKD using 2 different ADPKD mouse models. is an endogenously expressed form of duanyu1648 that has no membrane-anchoring domain, thereby giving it the ability to neutralize the ligands that stimulate duanyu1648 signals. Both overexpression of sduanyu1648 and sduanyu1648 treatment blocked cell proliferation in vitro. In addition, ADPKD mice showed reduced cysts accompanied by enhanced renal function, inhibition of cell proliferation, inflammation, and fibrosis. These positive therapeutic effects of sduanyu1648 displayed little liver toxicity, suggesting it as a new potential therapeutic target of ADPKD with low side effects.

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