Up-regulation of protease-activated receptor-1 in diabetic glomerulosclerosis.
Patients with diabetes are under a hypercoagulable state leading to generation of thrombin. It is not known whether thrombin plays a role in the progression of diabetic nephropathy. We analyzed gene expression of two thrombin receptors, protease-activated receptor-1 (PAR-1) and PAR-4 in the kidney of diabetic db/db mice. Mice developed hyperglycemia from 7 to 10 weeks of age and showed renal abnormalities such as mesangial expansion and urinary albumin excretion at 10 weeks of age. PAR-1 mRNA was up-regulated in isolated glomeruli in db/db mice compared with age-matched db/m littermates, but PAR-4 mRNA was not. In situ hybridization studies showed that PAR-1 mRNA was detected mainly at the glomerulus, and that intensive signals were observed in mesangial cells and podocytes. The up-regulation of PAR-1 in glomeruli in diabetic mice may play a role in the progression of glomerulosclerosis and abnormal urinary albumin excretion in diabetic nephropathy.
Sakai
Takumi
T
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba 300-2611, Japan. takumi_sakai@merck.com
Nambu
Tadahiro
T
Katoh
Masahiro
M
Uehara
Sayuri
S
Fukuroda
Takahiro
T
Nishikibe
Masaru
M
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000002:abnormalities / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
D012333:RNA, Messenger; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin