The Effect of FR167653, p38 Mitogen-Activated Protein Kinase (MAPK) Inhibitor, on the Expression of Slit Diaphragm-Associated Proteins in Experimental Diabetic Nephropathy.
- Author:
Dong Ryeol RYU
1
;
Tae Hyun YOO
;
Dong Sub JUNG
;
Seung Jae KWAK
;
Je Hyun PARK
;
Sun Ha LEE
;
Jin ji LEE
;
Jung Hwa RYU
;
Mina YU
;
Seung Jung KIM
;
Duk Hee KANG
;
Kyu Bok CHOI
;
Kyun Il YOON
;
Dae Suk HAN
;
Shin Wook KANG
Author Information
1. Department of Internal Medicine, School of Medicine, Ewha Womans University, Korea..
- Publication Type:Original Article
- Keywords:
Diabetic nephropathy;
p38 mitogen-activated protein kinases;
FR167653
- MeSH:
Albuminuria;
Animals;
Blotting, Western;
Cadherins;
Diabetic Nephropathies;
Enzyme-Linked Immunosorbent Assay;
Membrane Proteins;
p38 Mitogen-Activated Protein Kinases;
Protein Kinases;
Proteins;
Pyrazoles;
Pyridines;
Rats;
Rats, Sprague-Dawley;
Real-Time Polymerase Chain Reaction;
RNA, Messenger;
Streptozocin
- From:Korean Journal of Nephrology
2008;27(3):280-289
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: This study was undertaken to investigate the effect of a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor, FR167653, on urinary albumin excretion and on the expression of slit diaphragm-associated proteins in diabetic rats. METHODS: Thirty-two Sprague-Dawley rats were injected with diluent [control (C), N=16] or streptozotocin intraperitoneally (DM, N=16). Eight rats from each group were treated with 5 mg/kg/day FR 167653 (C+FR, DM+FR) for 6 weeks. At the time of sacrifice, 24-hour urinary albumin excretion was determined by ELISA. Glomerular nephrin, P-cadherin, and ZO-1 mRNA and protein expression were determined by real-time PCR and Western blot, respectively, with sieved glomeruli. RESULTS: Urinary albumin excretion was significantly higher in DM compared to C rats, and this increase in albuminuria was significantly inhibited by the administration of FR167653 in DM rats. Glomerular phospho-p38 MAPK protein expression was significantly increased in DM rats compared to C rats, and FR167653 treatment significantly attenuated the increase in phospho-p38 MAPK expression in DM glomeruli. Nephrin mRNA and protein expression were higher in 6-week DM compared to C glomeruli, and these increases were significantly abrogated with FR167653 treatment in DM rats. In contrast, FR167653 had no effects on the decrease in P-cadherin expression and the increase in ZO-1 expression observed in DM glomeruli. CONCLUSION: These findings suggest that FR167653, a p38 MAPK inhibitor, reduce the amount of albuminuria in early diabetic nephropathy, and this anti-proteinuric effect seems to be related with the change of glomerular nephrin expression.
