Genetic variation of the heparan sulfate proteoglycan gene (perlecan gene). Association with urinary albumin excretion in IDDM patients.
نویسندگان
چکیده
Both in patients with IDDM (1) and in healthy control subjects (2,3), increased urinary albumin excretion rate (AER) is associated with high relative morbidity and mortality. In IDDM patients, genetic susceptibility factors are most likely contributing to an increased AER (4,5) resulting in a cumulative incidence of nephropathy (AER >300 mg/24 h) of -30% (6). So far, candidate genes, proposed as susceptibility markers linked to abnormal albuminuria, have been identified because of the knowledge of pathophysiological events related to diabetic nephropathy. Heparan sulfate proteoglycan (HSPG, i.e., Perlecan) constitutes an integrated part of the glomerular basement membrane. It consists of a central core protein to which anionic sulfated polysaccharide chains (heparan sulfate [HS]) are linked (7), thus contributing to the negative charge of the glomerular filtration barrier and thereby indirectly to the composition of the glomerular filtration product (8,9). In IDDM patients, it has been demonstrated that increased AER is reduced by the administration of heparin (10) most likely because of a stimulating effect on the HS synthesis (11). The aim of the present study was for the first time to identify and characterize polymorphisms within the HSPG gene (HSPG2) and subsequently evaluate a possible association between such markers and nephropathy in a case-control study design comprising large groups of Caucasian IDDM patients with and without diabetic nephropathy from Denmark and U.K. The Danish population comprised 260
منابع مشابه
Heparan sulfate of perlecan is involved in glomerular filtration.
Perlecan is a heparan sulfate proteoglycan and a major component of the glomerular basement membrane. To understand the role of heparan sulfate chains of perlecan in glomerular filtration, detailed analyses were performed of the kidneys of Hspg2(Delta)(3/)(Delta)(3) mice, whose perlecan lacks heparan sulfate attachment sites in N-terminal domain I. Macroscopic, histologic, and electron microsco...
متن کاملGlomerular filtration is normal in the absence of both agrin and perlecan-heparan sulfate from the glomerular basement membrane.
BACKGROUND For several decades, it has been thought that the glomerular basement membrane (GBM) provides a charge-selective barrier for glomerular filtration. However, recent evidence has presented challenges to this concept: selective removal of heparan sulfate (HS) moieties that impart a negative charge to the GBM causes little if any increase in proteinuria. Removal of agrin, the major GBM H...
متن کاملRecent insights into the structure and functions of heparan sulfate proteoglycans in the human glomerular basement membrane.
As the first barrier to be crossed on the way to urinary space, the glomerular basement membrane (GBM) plays a key role in renal function. The permeability of the GBM for a given molecule is highly dependent on its size, shape and charge. As early as 1980, the charge-selective permeability was demonstrated to relate to the electrostatic properties of covalently bound heparan sulfates (HS) withi...
متن کاملImmunohistochemical quantification of heparan sulfate proteoglycan and collagen IV in skeletal muscle capillary basement membranes of patients with diabetic nephropathy.
In IDDM patients, an increased permeability of the glomerular capillaries has been associated with a general loss of negatively charged heparan sulfate proteoglycans (HSPGs) within basement membranes (BMs). In the present study, we used immunohistochemical staining to quantify heparan sulfate (HS), HSPG core protein, and collagen IV in capillary basement membranes of skeletal muscle biopsies ta...
متن کاملImpaired angiogenesis, delayed wound healing and retarded tumor growth in perlecan heparan sulfate-deficient mice.
Perlecan, a modular proteoglycan carrying primary heparan sulfate (HS) side chains, is a major component of blood vessel basement membranes. It sequesters growth factors such as fibroblast growth factor 2 (FGF-2) and regulates the ligand-receptor interactions on the cell surface, and thus it has been implicated in the control of angiogenesis. Both stimulatory and inhibitory effects of perlecan ...
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ورودعنوان ژورنال:
- Diabetes
دوره 46 10 شماره
صفحات -
تاریخ انتشار 1997