Increased glucose increases glomerular basement membrane in metanephric culture

Bernstein, Jay; Cheng, Frank; Roszka, Joseph P.

doi:10.1007/bf00866877

Cited by 8 publications

(4 citation statements)

References 33 publications

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“…On the other hand, high glucose induced increases in collagen production by MC in these experiments, as previously reported 19 , 20 ) . High glucose may activate the polyol pathway increasing the glycosylation of proteins by nonenzymatic means, or stimulate second messenger pathways resulting in alterations in the synthesis or degradation of extracellular matrix proteins 41 ) .…”

Section: Discussionsupporting

confidence: 91%

Effect of Angiotensin Converting Enzyme Inhibitor on Collagen Production by Cultured Mesangial Cells

Ihm

Park

Ahn

et al. 1994

Korean J Intern Med

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Cultured mesangial cells (MC) express renin mRNA and generate angiotensin I, supporting the action of local renin-angiotensin system. Also angiotensin II may act like a growth factor and was reported to increase collagen production (CP) in cultured MC. Angiotensin converting enzyme inhibitor is suggested to attenuate development and advancement of glomerulosclerosis, mainly with its hemodynamic effects. Therefore, we investigated the direct effects of enalapril (E) on CP by cultured MC. Rat MC were cultured in DMEM media alone, or containing high glucose (HG: 25 mM) or soluble immune complex (IC) prepared with bovine gamma globulin (BGG) and anti-BGG, with or without E (0.2 ug/ml). CP was determined after 24 h by [3H] proline incorporation method. E significantly reduced CP by 43% in medium as compared with control (C)(C: 37,210±4,200 vs C+E: 21,350 ± 5,080 cpm/well, p<0.01). CP in medium increased in the presence of HG (123% of C) or IC (147% of C), which was, however, prevented with E (HG + E: 105% of C, IC+E: 116% of C). There were no differences of CP in cell layer between C (3,490±220 cpm/well) and C+E (3,340±190 cpm/well), and also no changes after, addition of E in HG or IC groups. In conclusion, E directly attenuates CP by MC, even in the presence of HG or IC, independently of its hemodynamic effects.

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Section: Discussionsupporting

confidence: 91%

Effect of Angiotensin Converting Enzyme Inhibitor on Collagen Production by Cultured Mesangial Cells

Ihm

Park

Ahn

et al. 1994

Korean J Intern Med

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“…That the diabetic milieu is sufficient to produce the changes, i. e. independent of any genetic predisposition, is strongly substantiated by studies in experimental diabetes [44]. Further, it is an interesting observation that glomerular cells in vitro produce more BM when they are exposed to high glucose [45,46]. Still, in addition to these fundamental mechanisms, other conditions that prevail in the diabetic state may play a contributing role.…”

Section: Causes Of Structural Changes In Diabetic Glomerulimentioning

confidence: 99%

Glomerular structural changes in Type 1 (insulin-dependent) diabetes mellitus: causes, consequences, and prevention

Østerby

1992

Diabetologia

143

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Diabetic nephropathy is caused primarily by advanced glomerulopathy, the renal expression of diabetic microangiopathy. With stereological methods a quantitative description of the structural changes is achieved. The glomerulopathy is characterized by an increase in basement membrane material: thickening of the capillary wall and an increase in mesangial volume relative to glomerular volume, comprising increase in matrix. Among groups of patients conformity between renal function stage and structure exists. The parameters measuring glomerulopathy are normal at the onset of diabetes; patients with normoalbuminuria may show slight basement membrane thickening, or normal parameters; the microalbuminuric group shows a measurable, but moderate glomerulopathy; patients with overt nephropathy have advanced lesions; at this stage heterogeneity among glomeruli makes the estimates weaker. Recent data indicate that the changes in peripheral basement membrane and in mesangial matrix develop in concert and both contribute to the early stage of glomerulopathy in patients with microalbuminuria. As to the consequences of the structural changes the mechanism of albuminuria is not clear. It is suggested that the early glomerulopathy entails other structural modifications, including formation of new vessels which may be the site of leakage. The marked deviations in glomerular filtration rate correspond well with estimates of filtration surface area: in the early hyperfunction state it is increased; in advanced nephropathy it is decreased, due to advanced glomerulopathy in conjunction with glomerular occlusion. The diabetic state is the necessary condition for the glomerulopathy. In relating structural changes to presumed contributing causes no supporting evidence of a relationship with glomerular hyperfunction or hypertrophy was observed. The structural parameters may be useful tools in clinical trials aiming at arresting the development of glomerulopathy, and thereby providing a prevention of diabetic nephropathy.

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“…The mechanisms whereby hyperglycemia adversely affects nephrogenesis are not clearly defined, which in part may be due to the fact that there have been a limited number of studies describing changes in the embryonic kidney in high glucose ambience [79,83,84,85]. Nevertheless, previous in vivo observations indicate that hyperglycemia in utero impairs nephrogenesis in rats, leading to a reduced number of nephrons in the embryonic kidney.…”

Section: Aldohexose(s)-induced Dysmorphogenesis Of the Embryonic Kidneymentioning

confidence: 97%

“…Also, day-13 embryos exposed to high glucose show poor development of the caudal portion of the body, and the embryonic metanephroi are either absent or rudimentary. These observations have prompted in vitro studies where morphogenesis in the embryonic kidneys exposed to d-glucose or its epimer d-mannose was investigated via a transfilter organ culture system [86], and diverse morphologic and biochemical changes were observed [79,83,84,85].…”

Section: Aldohexose(s)-induced Dysmorphogenesis Of the Embryonic Kidneymentioning

confidence: 99%

Hyperglycemia: its imminent effects on mammalian nephrogenesis

et al. 2005

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A sustained exposure of the mammalian embryo to very high glucose ambience is associated with a multitude of congenital birth defects, including those of the cardiovascular, CNS, skeletal and urogenital systems during the first 6-8 weeks of gestation in humans. These urogenital abnormalities may be associated with "caudal regression syndrome" or may occur alone in the form of partial or total renal agenesis. Similarly, an increase in the incidence of morphogenetic defects is observed in the offspring of streptozotocin-induced diabetic rats and mice, and also in non-obese diabetic mice. In certain cases, failure during the growth of the lower parts of embryos or newborn mice involving the genitourinary system has been observed in animals with severe diabetes. Investigators have utilized whole organ culture systems to delineate the mechanisms relevant to dysmorphogenesis of the embryonic metanephros. A marked dysmorphogenesis of the metanephros is observed upon treatment with a high concentration of D: -glucose. Associated with it are changes that include branching dysmorphogenesis of the ureteric bud iterations, reduced population of nascent nephrons, decreased expression of basement membrane proteoglycans, depletion of ATP stores, and fulminant apoptosis of the cells at the interface of mesenchyme and ureteric bud epithelium. The latter findings suggest that disruption of epithelial:mesenchymal interactions may be the major event responsible for the metanephric dysmorphogenesis induced by high glucose ambience.

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Increased glucose increases glomerular basement membrane in metanephric culture

Cited by 8 publications

References 33 publications

Effect of Angiotensin Converting Enzyme Inhibitor on Collagen Production by Cultured Mesangial Cells

Effect of Angiotensin Converting Enzyme Inhibitor on Collagen Production by Cultured Mesangial Cells

Glomerular structural changes in Type 1 (insulin-dependent) diabetes mellitus: causes, consequences, and prevention

Hyperglycemia: its imminent effects on mammalian nephrogenesis

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