Glucose enhances type IV collagen production in cultured rat glomerular mesangial cells

Haneda, Masakazu; Kikkawa, Ryuichi; Horide, Naoki; Togawa, Masaki; Koya, Daisuke; Kajiwara, Nobuyuki; Ooshima, Akira; Shigeta, Yukio

doi:10.1007/bf00418276

Cited by 127 publications

(62 citation statements)

References 10 publications

(12 reference statements)

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“…Recently, it was reported that proliferating glomerular mesangial cells synthesize extracellular matrix components similar to that seen in the glomerular mesangium in vivo [3]. Furthermore, increased production of collagen type IV [2,3], laminin [3] and fibronectin [3] has been reported in rat mesangial cells when grown in high glucose medium for 12 [2] or 7 [3] days, respectively. The latter observation concerning fibronectin is different from that which we observed and may be due to different experimental design since we measured fibronectin content after short incubation times during the logarithmic phase of growth (48 h).…”

Section: Discussionmentioning

confidence: 93%

“…Changes of mesangial matrix composition in diabetes mellitus have been reported recently [1]. Especially, increased synthesis of collagen type IV [2] and other matrix constituents [3] have been demonstrated in rat mesangial cells cultured in high glucose medium. Basement membrane associated heparan sulphate proteoglycan (HSPG) is believed to play a key role in the development of diabetic glomerulopathy.…”

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confidence: 99%

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Elevated glucose decreases the content of a basement membrane associated heparan sulphate proteoglycan in proliferating cultured porcine mesangial cells

et al. 1992

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Summary. The effect of elevated glucose concentrations on the synthesis of basement membrane components was invesH tigated in proliferating cultured porcine mesangial cells. Basement membrane associated heparan sulphate proteoglycan was determined by enzyme immunoassay with a specific antiserum recognizing the core protein of the heparan sulphate proteoglycan. When cells were exposed to increasing glucose concentrations up to 40 mmol/1, the heparan sulphate proteoglycan content was concomitantly decreased to 53 % when compared to cells cultured under normal glucose concentrations or in the presence of 40 mmol/1 sorbitol. The fibronectin content was essentially unchanged under these conditions. No significant effect of insulin on these basement membrane components was found. The results indicate that hyperglycaemia may be responsible for a decrease of mesangial heparan sulphate proteoglycan content in diabetes mellitus. This supports the view that loss of heparan sulphate proteoglycan may be an important step or even an initial event of mesangial alterations in diabetic glomerulopathy.

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Section: Discussionmentioning

confidence: 93%

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confidence: 99%

Elevated glucose decreases the content of a basement membrane associated heparan sulphate proteoglycan in proliferating cultured porcine mesangial cells

et al. 1992

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“…This difference in tissue response may reflect the constellation of cells present in myocardial capillaries (endothelial cells and pericytes) and glo-meruli, which contain epithelial cells in addition to endothelial and mesangial cells; previous studies from our laboratory have indicated that only the latter two cell types form type VI collagen, while all three synthesize type IV. Most previous investigations on the effect of glucose on collagen synthesis by cells in culture have focused on type IV and have found an approximately twofold increase in this protein, whether the elevated glucose was present during the entire growth period of endothelial [17,26] or mesangial [27][28][29] cells or when exposure of confluent glomerular epithelial, mesangial or endothelial cells was only for short periods of time [3,6]. The influence of elevated glucose on type VI collagen has previously been studied only with rat glomerular mesangial cells and in that system the extent of stimulation was similar for both types VI and IV collagens, even though marked differences were observed in other aspects of the response, with type VI reflecting more rapidly both increased and normalized glucose levels, and only type IV being enhanced by addition of the glucose metabolite pyruvate or by the presence of aldosterone or IGF-1 [3].…”

Section: Discussionmentioning

confidence: 99%

Effect of high glucose on formation of extracellular matrix components by cultured rat heart endothelial cells

Spiro

D'Autilia

1995

Diabetologia

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SummaryIn an attempt to define the basis for the microvascular changes observed in diabetic myocardium, a study was undertaken on the effect of elevated glucose on the synthesis by rat heart endothelial cells of the extracellular matrix components, types VI, IV and I collagen, as well as fibronectin. Confluent cultures of these cells, isolated by fluorescenceactivated cell sorting after treatment with rhodamine-labelled acetylated low density lipoprotein, showed a three to fivefold enhancement in the synthesis of type VI collagen after exposure for 48 h to high glucose (20 to 30 mmol/1), as determined by immunoblot analysis. Increased production of type IV collagen and fibronectin was also observed, but the change was smaller and no effect on type I collagen was found. Measurement of mRNA levels by hybridization with cDNA probes indicated that 48-h exposure to high glucose significantly increased the level of transcripts for type VI and IV collagens but not for type I collagen. While glucose consumption by endothelial cells in high glucose doubled in the initial 24-h period, utilization returned to normal by 48 h, concomitant with a reduction in GLUT1 transcript levels, suggesting that signals for stimulation of collagen synthesis must be active during the initial period of exposure to elevated glucose levels. [Diabetologia (1995) 38: 430-436] Key words Rat heart endothelial cells, type VI collagen, type IV collagen, type I collagen, fibronectin, GLUT1, high glucose.Previous studies from our laboratory have indicated that the periodic acid-Schiff (PAS)-reactive deposits which are observed in the myocardium in the alloxan diabetic rat are characterized by an accumulation of type VI collagen with little or no increase occurring in other components such as types IV and I collagen, fibronectin or laminin [1,2]. Although the cells responsible for this increased formation of type VI collagen in the heart in diabetes are not yet known, the presence of the PAS-positive deposits as well as type Received: 6 July 1994 and in revised form: 26 October 1994Corresponding author: Dr. M. L Spiro, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts, 02215, USA Abbreviations: SDS, Sodium dodecylsulphate; PBS, phosphate-buffered physiological saline; DMEM, Dulbecco's modified Eagle's medium; DEPC, diethylpyrocarbonate; PAS, periodic acid-Schiff.VI immunoreactivity surrounding the capillaries of the myocardium [1] suggest that the endothelial cells of these small blood vessels may be involved, particularly since the ability of endothelial cells to produce type VI collagen has already been demonstrated using homogeneous populations of cells cultured from the kidney glomerulus [3]. We have therefore undertaken in the present study an evaluation of the effect of high glucose on the capacity of endothelial cells isolated from rat ventricles to synthesize types VI, IV and I collagen, and fibronectin, employing immunoblotting techniques, and have also analysed the level of transcripts for these collagens by hybridization wi...

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“…Since our previous studies [6,7] and those of others [40,41] have indicated that high glucose initiates a series of events in mesangial cells which lead to the accelerated production of matrix components, the occurrence of two separate mechanisms of glucose entry provides expanded possibilities for regulation and channelling of metabolites. While it is generally appreciated that Na + can be the driving force in promoting the uptake of glucose by cells which have a coupled transporter, and indeed we have previously observed that in mesangial cells this ion stimulates glucose consumption as well as collagen synthesis [7], the converse of this mechanism, namely the enhancement of Na + flux by glucose, is rarely considered even though it has been experimentally demonstrated to occur in renal brush border membrane vesicles [42].…”

Section: Rna+-dependent ~ ~ Facilitativementioning

confidence: 97%

Glucose entry into rat mesangial cells is mediated by both Na+-coupled and facilitative transporters

Wakisaka

Spiro

et al. 1995

Diabetologia

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Summary Since previous studies from our laboratory have demonstrated that increased glucose consumption by cultured rat mesangial cells is accompanied by an accelerated production of type IV and type VI collagen, we have now examined the manner by which glucose is transported into these cells. A progressive stimulation of glucose uptake by the mesangial cells was observed with increasing concentrations of NaC1 so that at 145 mmol/1 about twice as much glucose entered the cells as in its absence (substituted by choline chloride). Moreover, since phlorizin inhibited the NaCl-promoted uptake of glucose and this salt was found to increase the accumulation of c~-methylglucoside in a manner which could not be duplicated by KC1 or mannitol, both Na+-coupled and facilitative glucose transporters appeared to be present in the cells. K m values of 1.93 mmol/1 and 1.36 mmol/1 were determined for the co-transport and facilitated transport pathways, respectively, with their Vma X being 29.5 and 18.0 nmol. mg protein-1.h-1. Both uptake activities were found to be downregulated by exposure of the cells to high glucose and furthermore the Na+-dependent transport could no longer be detected after about 12 passages of the cells. Hybridization of mesangial cell mRNA with cDNA probes revealed transcripts for the Na+/glucose co-transporter as well as GLUT1 and to a lesser extent GLUT4. The identification of the co-transporter in these non-polarized cells is pertinent to an understanding of the intracellular signals which can lead to the development of the diabetic glomerular lesions; in the hyperglycaemic state this carrier provides an additional route for accelerated glucose entry and furthermore by the attendant increase in Na + flux may bring about an alteration in the ionic composition of the cell. [Diabetologia (1995) Although it has become evident that increased deposits of type IV as well as type VI collagen occur in the diabetic glomerulus [4,5] and that mesangial cells in culture demonstrate enhanced production of these two proteins in response to elevated glucose levels [6,7], the mechanism by which glucose and its metabolites regulate the synthesis of the glomerular extracellular matrix remains obscure. Only very limited information is currently available in regard to the manner of entry and subsequent metabolism of glucose by mesangial cells, a subject which is crucial to the understanding of the metabolic hypothesis of diabetic glomerulopathy.In an attempt to fill this void in knowledge and prompted by our recent observation that mesangial

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Glucose enhances type IV collagen production in cultured rat glomerular mesangial cells

Cited by 127 publications

References 10 publications

Elevated glucose decreases the content of a basement membrane associated heparan sulphate proteoglycan in proliferating cultured porcine mesangial cells

Elevated glucose decreases the content of a basement membrane associated heparan sulphate proteoglycan in proliferating cultured porcine mesangial cells

Effect of high glucose on formation of extracellular matrix components by cultured rat heart endothelial cells

Glucose entry into rat mesangial cells is mediated by both Na+-coupled and facilitative transporters

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