title: Targeting of receptor for advanced glycation end products suppresses cyst growth in polycystic kidney disease.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder. Although a myriad of research groups have attempted to identify a new therapeutic target for ADPKD, no drug has worked well in clinical trials. Our research group has focused on the receptor for advanced glycation end products (RAGE) gene as a novel target for ADPKD. This gene is involved in inflammation and cell proliferation. We have already confirmed that blocking RAGE function attenuates cyst growth in vitro. Based on this previous investigation, our group examined the effect of RAGE on cyst enlargement in vivo. PC2R mice, a severe ADPKD mouse model that we generated, were utilized. An adenovirus containing anti-RAGE shRNA was injected intravenously into this model. We observed that RAGE gene knockdown resulted in loss of kidney weight and volume. Additionally, the cystic area that originated from different nephron segments decreased in size because of down-regulation of the RAGE gene. Blood urea nitrogen and creatinine values tended to be lower after inhibiting RAGE. Based on these results, we confirmed that the RAGE gene could be an effective target for ADPKD treatment.
authors: From the Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea and.
authors: Eun Young
authors: EY
authors: Park
authors: Bo Hye
authors: BH
authors: Kim
authors: Eun Ji
authors: EJ
authors: Lee
authors: EunSun
authors: E
authors: Chang
authors: Dae Won
authors: DW
authors: Kim
authors: Soo Young
authors: SY
authors: Choi
authors: Jong Hoon
authors: JH
authors: Park
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D003560:Cysts / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007677:Kidney Function Tests; D051379:Mice; D058990:Molecular Targeted Therapy; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000091283:Protein Kinase D2; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011494:Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Adenovirus; Cystic Disease; Cystogenesis; Inflammation; Kidney; Proliferation; Receptor for Advanced Glycation End Products (RAGE); Transgenic Mice