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: Qiao-Yan Guo, Li-Ning Miao, Bing Li, Fu-Zhe Ma, Nian Liu, Lu Cai, Zhong-Gao Xu
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 300 Issue 4 Pg. E708-16 (Apr 2011) ISSN: 1522-1555 [Electronic] United States
• PMID: 21285403 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• Hydroxyeicosatetraenoic Acids
• Receptor, Angiotensin, Type 1
• Angiotensin II
• Streptozocin
• Arachidonate 12-Lipoxygenase

Topics

• Angiotensin II (pharmacology)
• Animals
• Arachidonate 12-Lipoxygenase (genetics, metabolism, physiology)
• Cadherins (genetics, metabolism)
• Diabetes Mellitus, Experimental (chemically induced, genetics, metabolism, pathology)
• Diabetes Mellitus, Type 2 (complications, genetics, metabolism, pathology)
• Down-Regulation (drug effects)
• Gene Expression Regulation (drug effects)
• Hydroxyeicosatetraenoic Acids (pharmacology)
• Kidney Glomerulus (drug effects, metabolism, pathology)
• Male
• Organ Size (genetics, physiology)
• Proteinuria (etiology)
• Rats
• Rats, Wistar
• Receptor, Angiotensin, Type 1 (genetics, metabolism)
• Streptozocin
• Up-Regulation (drug effects, genetics)