title: Role of 12-lipoxygenase in decreasing P-cadherin and increasing angiotensin II type 1 receptor expression according to glomerular size in type 2 diabetic rats.
abstract: 12-lipoxygenase (12-LO) was implicated in the development of diabetic nephropathy (DN), in which the proteinuria was thought to be associated with a decreased expression of glomerular P-cadherin. Therefore, we investigated the role of 12-LO in the glomerular P-cadherin expression in type 2 diabetic rats according to the glomerular sizes. Rats fed with high-fat diet for 6 wk were treated with low-dose streptozotocin. Once diabetes onset, diabetic rats were treated with 12-LO inhibitor cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC) for 8 wk. Then glomeruli were isolated from diabetic and control rats with a sieving method. RT-PCR, Western blotting, and immunofluorescent staining were used for mRNA and protein expressions of P-cadherin and angiotensin II (Ang II) type 1 receptor (AT1). We found that CDC did not affect the glucose levels but completely attenuated diabetic increases in glomerular volume and proteinuria. Diabetes significantly decreased the P-cadherin mRNA and protein expressions and increased the AT1 mRNA and protein expressions in the glomeruli. These changes were significantly prevented by CDC and recaptured by direct infusion of 12-LO product [12(S)-HETE] to normal rats for 7 days. The decreased P-cadherin expression was similar between large and small glomeruli, but the increased AT1 expression was significantly higher in the large than in the small glomeruli from diabetic and 12(S)-HETE-treated rats. Direct infusion of normal rats with Ang II for 14 days also significantly decreased the glomerular P-cadherin expression. These results suggest that diabetic proteinuria is mediated by the activation of 12-LO pathway that is partially attributed to the decreased glomerular P-cadherin expression.
authors.affiliation: Dept. of Nephrology, Second Hospital of Jilin University, Changchun, China.
authors.forename: Qiao-Yan
authors.initials: QY
authors.lastname: Guo
authors.forename: Li-Ning
authors.initials: LN
authors.lastname: Miao
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Fu-Zhe
authors.initials: FZ
authors.lastname: Ma
authors.forename: Nian
authors.initials: N
authors.lastname: Liu
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.forename: Zhong-Gao
authors.initials: ZG
authors.lastname: Xu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009929:Organ Size / Q000235:genetics / Q000502:physiology; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D013311:Streptozocin; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D015820:Cadherins; D006893:Hydroxyeicosatetraenoic Acids; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D013311:Streptozocin; D001092:Arachidonate 12-Lipoxygenase