Mechanical stretch induces podocyte hypertrophy in vitro

Arndt T. Petermann, Jeffrey Pippin, Raghu Durvasula, Raimund Pichler, Eeiju Hiromura, Toshiaki Monkawa, William G. Couser, Stuart J. Shankland

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Background. Increased intraglomerular pressure is a final pathway toward glomerulosclerosis in systemic hypertension, diabetes, and focal segmental glomerulosclerosis (FSGS). Increased intraglomerular pressure causes stress-tension, or stretch, on resident glomerular cells. However, the effects of stretch on podocyte growth, and the mechanisms that underlie this, have not been elucidated. Methods. To test the hypothesis that stretch alters podocyte growth, cultured mouse podocytes were exposed to cyclic mechanical stretch created by vacuum; control cells were grown under similar conditions, but not exposed to stretch. Proliferation (cell cycle phases) and hypertrophy (forward light scatter) were measured in stretched and control podocytes by flow cytometry. The role of the cyclin-dependent kinase (CDK) inhibitors, p21 and p27, was examined by stretching podocytes isolated from p21 and p27 knockout (-/-) mice, and the role of specific signaling pathways was assessed by Western blot analysis and blocking studies. Results. Our results showed that stretch reduced cell cycle progression in wild-type and single p27-/- podocytes and induced hypertrophy in these cells in all phases of the cell cycle at 24, 48, and 72 hours. In contrast, stretch did not induce hypertrophy in single p21-/- and double p21/p27-/- podocytes. Stretch-induced hypertrophy required cell cycle entry, and was prevented by specifically blocking extracellular signal-regulated kinase 1/2 (Erk1/2) or Akt. Although stretch increased p38 activation, inhibition of this pathway had no effect on hypertrophy. Conclusion. Mechanical stretch induces hypertrophy in podocytes in vitro in all phases of the cell cycle. This effect is cell cycle dependent, and requires p21, Erk1/2, and Akt. Stretch may play a role in podocyte injury when intraglomerular pressure is increased.

Original languageEnglish
Pages (from-to)157-166
Number of pages10
JournalKidney International
Volume67
Issue number1
DOIs
Publication statusPublished - 2005 Jan
Externally publishedYes

Fingerprint

Podocytes
Hypertrophy
Cell Cycle
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Pressure
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
In Vitro Techniques
Focal Segmental Glomerulosclerosis
Growth
Vacuum
Knockout Mice
Flow Cytometry
Western Blotting
Hypertension
Light

Keywords

  • Cell cycle
  • Cyclin-dependent kinase
  • Hypertrophy
  • Kidney
  • Mechanical stress
  • Podocyte
  • Stretch

ASJC Scopus subject areas

  • Nephrology

Cite this

Petermann, A. T., Pippin, J., Durvasula, R., Pichler, R., Hiromura, E., Monkawa, T., ... Shankland, S. J. (2005). Mechanical stretch induces podocyte hypertrophy in vitro. Kidney International, 67(1), 157-166. https://doi.org/10.1111/j.1523-1755.2005.00066.x

Mechanical stretch induces podocyte hypertrophy in vitro. / Petermann, Arndt T.; Pippin, Jeffrey; Durvasula, Raghu; Pichler, Raimund; Hiromura, Eeiju; Monkawa, Toshiaki; Couser, William G.; Shankland, Stuart J.

In: Kidney International, Vol. 67, No. 1, 01.2005, p. 157-166.

Research output: Contribution to journalArticle

Petermann, AT, Pippin, J, Durvasula, R, Pichler, R, Hiromura, E, Monkawa, T, Couser, WG & Shankland, SJ 2005, 'Mechanical stretch induces podocyte hypertrophy in vitro', Kidney International, vol. 67, no. 1, pp. 157-166. https://doi.org/10.1111/j.1523-1755.2005.00066.x
Petermann AT, Pippin J, Durvasula R, Pichler R, Hiromura E, Monkawa T et al. Mechanical stretch induces podocyte hypertrophy in vitro. Kidney International. 2005 Jan;67(1):157-166. https://doi.org/10.1111/j.1523-1755.2005.00066.x
Petermann, Arndt T. ; Pippin, Jeffrey ; Durvasula, Raghu ; Pichler, Raimund ; Hiromura, Eeiju ; Monkawa, Toshiaki ; Couser, William G. ; Shankland, Stuart J. / Mechanical stretch induces podocyte hypertrophy in vitro. In: Kidney International. 2005 ; Vol. 67, No. 1. pp. 157-166.
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abstract = "Background. Increased intraglomerular pressure is a final pathway toward glomerulosclerosis in systemic hypertension, diabetes, and focal segmental glomerulosclerosis (FSGS). Increased intraglomerular pressure causes stress-tension, or stretch, on resident glomerular cells. However, the effects of stretch on podocyte growth, and the mechanisms that underlie this, have not been elucidated. Methods. To test the hypothesis that stretch alters podocyte growth, cultured mouse podocytes were exposed to cyclic mechanical stretch created by vacuum; control cells were grown under similar conditions, but not exposed to stretch. Proliferation (cell cycle phases) and hypertrophy (forward light scatter) were measured in stretched and control podocytes by flow cytometry. The role of the cyclin-dependent kinase (CDK) inhibitors, p21 and p27, was examined by stretching podocytes isolated from p21 and p27 knockout (-/-) mice, and the role of specific signaling pathways was assessed by Western blot analysis and blocking studies. Results. Our results showed that stretch reduced cell cycle progression in wild-type and single p27-/- podocytes and induced hypertrophy in these cells in all phases of the cell cycle at 24, 48, and 72 hours. In contrast, stretch did not induce hypertrophy in single p21-/- and double p21/p27-/- podocytes. Stretch-induced hypertrophy required cell cycle entry, and was prevented by specifically blocking extracellular signal-regulated kinase 1/2 (Erk1/2) or Akt. Although stretch increased p38 activation, inhibition of this pathway had no effect on hypertrophy. Conclusion. Mechanical stretch induces hypertrophy in podocytes in vitro in all phases of the cell cycle. This effect is cell cycle dependent, and requires p21, Erk1/2, and Akt. Stretch may play a role in podocyte injury when intraglomerular pressure is increased.",
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AU - Petermann, Arndt T.

AU - Pippin, Jeffrey

AU - Durvasula, Raghu

AU - Pichler, Raimund

AU - Hiromura, Eeiju

AU - Monkawa, Toshiaki

AU - Couser, William G.

AU - Shankland, Stuart J.

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N2 - Background. Increased intraglomerular pressure is a final pathway toward glomerulosclerosis in systemic hypertension, diabetes, and focal segmental glomerulosclerosis (FSGS). Increased intraglomerular pressure causes stress-tension, or stretch, on resident glomerular cells. However, the effects of stretch on podocyte growth, and the mechanisms that underlie this, have not been elucidated. Methods. To test the hypothesis that stretch alters podocyte growth, cultured mouse podocytes were exposed to cyclic mechanical stretch created by vacuum; control cells were grown under similar conditions, but not exposed to stretch. Proliferation (cell cycle phases) and hypertrophy (forward light scatter) were measured in stretched and control podocytes by flow cytometry. The role of the cyclin-dependent kinase (CDK) inhibitors, p21 and p27, was examined by stretching podocytes isolated from p21 and p27 knockout (-/-) mice, and the role of specific signaling pathways was assessed by Western blot analysis and blocking studies. Results. Our results showed that stretch reduced cell cycle progression in wild-type and single p27-/- podocytes and induced hypertrophy in these cells in all phases of the cell cycle at 24, 48, and 72 hours. In contrast, stretch did not induce hypertrophy in single p21-/- and double p21/p27-/- podocytes. Stretch-induced hypertrophy required cell cycle entry, and was prevented by specifically blocking extracellular signal-regulated kinase 1/2 (Erk1/2) or Akt. Although stretch increased p38 activation, inhibition of this pathway had no effect on hypertrophy. Conclusion. Mechanical stretch induces hypertrophy in podocytes in vitro in all phases of the cell cycle. This effect is cell cycle dependent, and requires p21, Erk1/2, and Akt. Stretch may play a role in podocyte injury when intraglomerular pressure is increased.

AB - Background. Increased intraglomerular pressure is a final pathway toward glomerulosclerosis in systemic hypertension, diabetes, and focal segmental glomerulosclerosis (FSGS). Increased intraglomerular pressure causes stress-tension, or stretch, on resident glomerular cells. However, the effects of stretch on podocyte growth, and the mechanisms that underlie this, have not been elucidated. Methods. To test the hypothesis that stretch alters podocyte growth, cultured mouse podocytes were exposed to cyclic mechanical stretch created by vacuum; control cells were grown under similar conditions, but not exposed to stretch. Proliferation (cell cycle phases) and hypertrophy (forward light scatter) were measured in stretched and control podocytes by flow cytometry. The role of the cyclin-dependent kinase (CDK) inhibitors, p21 and p27, was examined by stretching podocytes isolated from p21 and p27 knockout (-/-) mice, and the role of specific signaling pathways was assessed by Western blot analysis and blocking studies. Results. Our results showed that stretch reduced cell cycle progression in wild-type and single p27-/- podocytes and induced hypertrophy in these cells in all phases of the cell cycle at 24, 48, and 72 hours. In contrast, stretch did not induce hypertrophy in single p21-/- and double p21/p27-/- podocytes. Stretch-induced hypertrophy required cell cycle entry, and was prevented by specifically blocking extracellular signal-regulated kinase 1/2 (Erk1/2) or Akt. Although stretch increased p38 activation, inhibition of this pathway had no effect on hypertrophy. Conclusion. Mechanical stretch induces hypertrophy in podocytes in vitro in all phases of the cell cycle. This effect is cell cycle dependent, and requires p21, Erk1/2, and Akt. Stretch may play a role in podocyte injury when intraglomerular pressure is increased.

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KW - Mechanical stress

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