The Effects of High Glucose Concentration on Angiotensin II- Or Transforming Growth Factor-β-Induced DNA Synthesis, Hypertrophy and Collagen Synthesis in Cultured Rat Mesangial Cells

Kyu Hun Choi, Shin-Wook Kang, Ho Yung Lee, Dae Suk Han

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Abstract

Hyperglycemia is a principal characteristic of diabetes, and has an influence on many cellular functions. In order to investigate whether the intracellular signaling pathways inducing proliferation, hypertrophy and matrix synthesis of mesangial cells are altered in a diabetic environment, we evaluated the effects of a high concentration of extracellular glucose(25 mM; 450 mg/dl) on [3H]thymidine uptake, hypertrophy, and [3H]proline incorporation into a collagenase-sensitive protein, induced by angiotensin II(Ang II) or transforming growth factor(TGF)-β, in cultured rat mesangial cells. The exposure to a high glucose concentration for 7 days significantly inhibited Ang II(10-6 M)-induced [3H]thymidine uptake, compared to normal glucose concentration(5 mM)(M±S.D., 1050± 100 cpm/well vs 550±97, p<0.05), and markedly prevented the inhibition of [3H]thymidine uptake by TGF-β(1 ng/ml)(132±10 vs 340±67, p<0.05). The administration of H-7(50 μM), a protein kinose C(PKC) inhibitor, did not reverse these effects of high glucose on [3H]thymidine uptake. On flow cytometric analysis of cell size, the mean cell size was significantly greater for the cells exposed to high glucose or treated with Ang II or TGF-β, compared to that for the untreated cells. But the addition of Ang II or TGF-β to the cells exposed to high glucose did not show further enlargement in size. The exposure to high glucose and the treatment with Ang II or TGF-β significantly increased collagen synthesis, measured by [3H]proline incorporation. The Ang II- or TGF-β-induced increase of [3H]proline incorporation did not show changes under high glucose culture condition, compared to normal glucose concentration(Ang II, 27880±3560 cpm vs 26978±2284, TGF-β, 26559± 3700 vs 25800±1660, p>0.05). In conclusion, although the signaling pathway for DNA synthesis by Ang II or TGF-β are influenced, possibly mediated by PKC-independent mechanism(s), the pathway inducing hypertrophy or collagen synthesis by both agents appears to be unchanged under the high extracellular glucose concentration in cultured rat mesangial cells.

Original languageEnglish
Pages (from-to)302-311
Number of pages10
JournalYonsei Medical Journal
Volume37
Issue number5
DOIs
Publication statusPublished - 1996 Jan 1

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Mesangial Cells
Transforming Growth Factors
Angiotensin II
Hypertrophy
Collagen
Glucose
DNA
Thymidine
Collagenases
Proline
Hyperglycemia
Proteins

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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title = "The Effects of High Glucose Concentration on Angiotensin II- Or Transforming Growth Factor-β-Induced DNA Synthesis, Hypertrophy and Collagen Synthesis in Cultured Rat Mesangial Cells",
abstract = "Hyperglycemia is a principal characteristic of diabetes, and has an influence on many cellular functions. In order to investigate whether the intracellular signaling pathways inducing proliferation, hypertrophy and matrix synthesis of mesangial cells are altered in a diabetic environment, we evaluated the effects of a high concentration of extracellular glucose(25 mM; 450 mg/dl) on [3H]thymidine uptake, hypertrophy, and [3H]proline incorporation into a collagenase-sensitive protein, induced by angiotensin II(Ang II) or transforming growth factor(TGF)-β, in cultured rat mesangial cells. The exposure to a high glucose concentration for 7 days significantly inhibited Ang II(10-6 M)-induced [3H]thymidine uptake, compared to normal glucose concentration(5 mM)(M±S.D., 1050± 100 cpm/well vs 550±97, p<0.05), and markedly prevented the inhibition of [3H]thymidine uptake by TGF-β(1 ng/ml)(132±10 vs 340±67, p<0.05). The administration of H-7(50 μM), a protein kinose C(PKC) inhibitor, did not reverse these effects of high glucose on [3H]thymidine uptake. On flow cytometric analysis of cell size, the mean cell size was significantly greater for the cells exposed to high glucose or treated with Ang II or TGF-β, compared to that for the untreated cells. But the addition of Ang II or TGF-β to the cells exposed to high glucose did not show further enlargement in size. The exposure to high glucose and the treatment with Ang II or TGF-β significantly increased collagen synthesis, measured by [3H]proline incorporation. The Ang II- or TGF-β-induced increase of [3H]proline incorporation did not show changes under high glucose culture condition, compared to normal glucose concentration(Ang II, 27880±3560 cpm vs 26978±2284, TGF-β, 26559± 3700 vs 25800±1660, p>0.05). In conclusion, although the signaling pathway for DNA synthesis by Ang II or TGF-β are influenced, possibly mediated by PKC-independent mechanism(s), the pathway inducing hypertrophy or collagen synthesis by both agents appears to be unchanged under the high extracellular glucose concentration in cultured rat mesangial cells.",
author = "Choi, {Kyu Hun} and Shin-Wook Kang and Lee, {Ho Yung} and Han, {Dae Suk}",
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AU - Choi, Kyu Hun

AU - Kang, Shin-Wook

AU - Lee, Ho Yung

AU - Han, Dae Suk

PY - 1996/1/1

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N2 - Hyperglycemia is a principal characteristic of diabetes, and has an influence on many cellular functions. In order to investigate whether the intracellular signaling pathways inducing proliferation, hypertrophy and matrix synthesis of mesangial cells are altered in a diabetic environment, we evaluated the effects of a high concentration of extracellular glucose(25 mM; 450 mg/dl) on [3H]thymidine uptake, hypertrophy, and [3H]proline incorporation into a collagenase-sensitive protein, induced by angiotensin II(Ang II) or transforming growth factor(TGF)-β, in cultured rat mesangial cells. The exposure to a high glucose concentration for 7 days significantly inhibited Ang II(10-6 M)-induced [3H]thymidine uptake, compared to normal glucose concentration(5 mM)(M±S.D., 1050± 100 cpm/well vs 550±97, p<0.05), and markedly prevented the inhibition of [3H]thymidine uptake by TGF-β(1 ng/ml)(132±10 vs 340±67, p<0.05). The administration of H-7(50 μM), a protein kinose C(PKC) inhibitor, did not reverse these effects of high glucose on [3H]thymidine uptake. On flow cytometric analysis of cell size, the mean cell size was significantly greater for the cells exposed to high glucose or treated with Ang II or TGF-β, compared to that for the untreated cells. But the addition of Ang II or TGF-β to the cells exposed to high glucose did not show further enlargement in size. The exposure to high glucose and the treatment with Ang II or TGF-β significantly increased collagen synthesis, measured by [3H]proline incorporation. The Ang II- or TGF-β-induced increase of [3H]proline incorporation did not show changes under high glucose culture condition, compared to normal glucose concentration(Ang II, 27880±3560 cpm vs 26978±2284, TGF-β, 26559± 3700 vs 25800±1660, p>0.05). In conclusion, although the signaling pathway for DNA synthesis by Ang II or TGF-β are influenced, possibly mediated by PKC-independent mechanism(s), the pathway inducing hypertrophy or collagen synthesis by both agents appears to be unchanged under the high extracellular glucose concentration in cultured rat mesangial cells.

AB - Hyperglycemia is a principal characteristic of diabetes, and has an influence on many cellular functions. In order to investigate whether the intracellular signaling pathways inducing proliferation, hypertrophy and matrix synthesis of mesangial cells are altered in a diabetic environment, we evaluated the effects of a high concentration of extracellular glucose(25 mM; 450 mg/dl) on [3H]thymidine uptake, hypertrophy, and [3H]proline incorporation into a collagenase-sensitive protein, induced by angiotensin II(Ang II) or transforming growth factor(TGF)-β, in cultured rat mesangial cells. The exposure to a high glucose concentration for 7 days significantly inhibited Ang II(10-6 M)-induced [3H]thymidine uptake, compared to normal glucose concentration(5 mM)(M±S.D., 1050± 100 cpm/well vs 550±97, p<0.05), and markedly prevented the inhibition of [3H]thymidine uptake by TGF-β(1 ng/ml)(132±10 vs 340±67, p<0.05). The administration of H-7(50 μM), a protein kinose C(PKC) inhibitor, did not reverse these effects of high glucose on [3H]thymidine uptake. On flow cytometric analysis of cell size, the mean cell size was significantly greater for the cells exposed to high glucose or treated with Ang II or TGF-β, compared to that for the untreated cells. But the addition of Ang II or TGF-β to the cells exposed to high glucose did not show further enlargement in size. The exposure to high glucose and the treatment with Ang II or TGF-β significantly increased collagen synthesis, measured by [3H]proline incorporation. The Ang II- or TGF-β-induced increase of [3H]proline incorporation did not show changes under high glucose culture condition, compared to normal glucose concentration(Ang II, 27880±3560 cpm vs 26978±2284, TGF-β, 26559± 3700 vs 25800±1660, p>0.05). In conclusion, although the signaling pathway for DNA synthesis by Ang II or TGF-β are influenced, possibly mediated by PKC-independent mechanism(s), the pathway inducing hypertrophy or collagen synthesis by both agents appears to be unchanged under the high extracellular glucose concentration in cultured rat mesangial cells.

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