Synergistic contributions of carbonyl stress and megsin in diabetic nephropathy.
Diabetic nephropathy is the most common cause of end-stage renal failure. The primary glomerular changes in diabetic nephropathy are diffuse and nodular glomerulosclerosis, manifested by an increase in mesangial matrix. Research has demonstrated that advanced glycation end products (AGEs), oxidative stress, and carbonyl stress might play a crucial role in the pathogenesis of diabetic nephropathy via multiple mechanisms. AGEs augment extracellular matrix synthesis, contribute to the release of proinflammatory cytokines and expression of growth factors and adhesion molecules, and interact with the renin-angiotensin system. Megsin is a novel serine protease inhibitor predominantly expressed in mesanguim. Megsin is upregulated in kidney samples of patients with diabetic nephropathy. Transgenic mice overexpressing megsin spontaneously develop kidney disease characterized by mesangial injury. Megsin is likely to contribute to mesangial injury in the process of diabetic nephropathy. Lack of appropriate animal models has hampered understanding the pathogenesis of diabetic nephropathy and development of effective therapies. Megsin and AGEs are suitable targets for new drugs of diabetic nephropathy and for the development of appropriate animal models of diabetic nephropathy.
Inagi
Reiko
R
Institute of Medical Sciences, Tokai University School of Medicine, Kanagawa 259-1193, Japan.
Nangaku
Masaomi
M
Miyata
Toshio
T
D000818:Animals; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology; D015843:Serpins / Q000502:physiology*
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C114170:SERPINB7 protein, human; D015843:Serpins