Collectrin, a novel homolog of angiotensin-converting enzyme-related carboxypeptidase (ACE2), was identified during polymerase chain reaction-based cDNA subtraction and up-regulated in 5/6 ablated kidneys at hypertrophic phase. Collectrin, with 222 amino acids, has an apparent signal peptide and a transmembrane domain; the sequence is conserved in mouse, rat, and human and shares 81.9% identity. Human collectrin has 47.8% identity with non-catalytic extracellular, transmembrane, and cytosolic domains of ACE2; however, unlike ACE and ACE2, collectrin lacks active dipeptidyl carboxypeptidase catalytic domains. The collectrin mRNA transcripts are expressed exclusively in the kidney. In situ hybridization reveals its mRNA expression in renal collecting ducts, and immunohistochemistry shows that it is localized to the luminal surface and cytoplasm of collecting ducts. Immunoprecipitation studies, using [35 S]methionine-labeled renal cortical and inner medullar collecting duct cells, i.e. M-1 and mIMCD-3, indicate that the protein size is ϳ32 kDa. During the development of mouse kidney, mRNA signal is detectable at day 13 of gestation, and the protein product is observed in the ureteric bud branches. Its expression is progressively increased during later stages of the gestation extending into the neonatal periods and then is decreased in adult life. Up-regulated expression of collectrin in the hypertrophic kidneys after renal ablation and restricted spatio-temporal expression during development indicates a possible role(s)in the process of progressive renal failure and renal organogenesis.

Despite the progress in the therapeutic treatment of diabetes mellitus, diabetic nephropathy is one of the major complications of diabetes and the single largest cause of endstage renal diseases. Histologically, early diabetic nephropathy is characterized by glomerular hypertrophy and the inappropriate dilatation of afferent arterioles, which are believed to be associated with hyperfiltration and are followed by thickening of the glomerular basement membrane and accumulation of mesangial matrix [1,2]. The pathogenesis of glomerular hypertrophy and afferent arteriolar dilatation due to diabetes is, however, still not clear.Nitric oxide (NO) has been identified as a pleiotropic intercellular messenger that regulates a variety of cellular functions [3] and an endothelium-derived relaxing factor that inhibits contraction of vascular smooth muscles, as well as the adhesion or aggregation of platelets [4]. Three isoforms of this enzyme have Diabetologia (1998) Summary The overproduction of nitric oxide (NO) is reported in the diabetic kidney and considered to be involved in glomerular hyperfiltration. The precise mechanism of NO production in the diabetic kidney is, however, not known. In this report, we compare the localization of endothelial cell nitric oxide synthase (ecNOS) isoform expression in the kidney tissue of streptozotocin (STZ)-induced diabetic rats and 5/6 nephrectomized rats and clarify the pivotal role of ecNOS for the glomerular hyperfiltration in the early stages of diabetic nephropathy. In diabetic rats, the diameters of afferent arterioles, the glomerular volume, creatinine clearance, and urinary NO 2 / NO 3 were increased after the induction of diabetes. Efferent arterioles were, however, not altered. Insulin or L-NAME treatment returned the diameters of afferent arterioles, glomerular volume, creatinine clearance, and urinary NO 2 /NO 3 to normal. The expression of ecNOS in afferent arterioles and glomeruli of diabetic rats increased during the early stages of the disease, but was not altered in efferent arterioles. Treatment with either insulin or L-NAME decreased ecNOS expression in afferent arterioles and in glomeruli. In contrast, the ecNOS expression was upregulated in both afferent and efferent arterioles and in the glomeruli of 5/6 nephrectomized rats, where the dilatation of afferent and efferent arterioles and glomerular enlargement were observed. Treatment with L-NAME ameliorated the ecNOS expression and dilatation of arterioles. We conclude that enhanced NO synthesis by ecNOS in afferent arterioles and glomerular endothelial cells in response to the hyperglycaemic state could cause preferential dilatation of afferent arterioles, which ultimately induces glomerular enlargement and glomerular hyperfiltration. [Diabetologia (1998 Keywords Nitric oxide (NO), endothelial cell nitric oxide synthase (ecNOS), diabetic nephropathy, afferent arterioles, glomerular hyperfiltration Received: 5 January 1998 and in revised form: 27 April 1998Corresponding author: H. Sugimoto MD., Department of Med...

Hyperglycemia is a major determinant of glomerulosclerosis in STZ-induced diabetic CD-1 mice, and the altered gene expression in the early phase of diabetic kidney may be critical for the development of diabetic nephropathy.

lation of macrophages that are involved in immune-mediated Efficacy of galectins in the amelioration of nephrotoxic serum glomerular diseases. nephritis in Wistar Kyoto rats.Background. Galectins are characterized by specific affinity for ␤-galactoside sugars, and they play a role in diverse biological processes, including cell adhesion, cell proliferation, and