Mycophenolate Mofetil Ameliorates Diabetic Nephropathy in db/db Mice.
Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Mycophenolate mofetil (MMF) has an anti-inflammatory effect, inhibiting lymphocyte proliferation. Previous studies showed attenuation of diabetic nephropathy with MMF, but the underlying mechanisms were unclear. This study aimed to identify the effect of MMF on diabetic nephropathy and investigate its action mechanisms in type 2 diabetic mice model. Eight-week-old db/db and control mice (db/m mice) received vehicle or MMF at a dose of 30 mg/kg/day for 12 weeks. MMF-treated diabetic mice showed decreased albuminuria, attenuated mesangial expansion, and profibrotic mRNA expressions despite the high glucose level. The number of infiltrated CD4(+) and CD8(+) T cells in the kidney was significantly decreased in MMF-treated db/db mice and it resulted in attenuating elevated intrarenal TNF-α and IL-17. The renal chemokines expression and macrophages infiltration were also attenuated by MMF treatment. The decreased expression of glomerular nephrin and WT1 was recovered with MMF treatment. MMF prevented the progression of diabetic nephropathy in db/db mice independent of glycemic control. These results suggest that the effects of MMF in diabetic nephropathy are mediated by CD4(+) T cell regulation and related cytokines.
Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Jung-Woo
JW
Seo
Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Yang Gyun
YG
Kim
Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Sang Ho
SH
Lee
Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Arah
A
Lee
Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Dong-Jin
DJ
Kim
Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Kyung-Hwan
KH
Jeong
Division of Cardiology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Kyung Hye
KH
Lee
Division of Cardiology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Seung Joon
SJ
Hwang
Division of Cardiology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Jong Shin
JS
Woo
Department of Pathology, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Sung Jig
SJ
Lim
Division of Cardiology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Weon
W
Kim
Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 134-727, Republic of Korea.
Ju-Young
JY
Moon
D000419:Albuminuria / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D009173:Mycophenolic Acid