An in vitro test of the cell stretch-proliferation hypothesis of renal cyst enlargement

G. A. Tanner, P. F. McQuillan, M. R. Maxwell, J. K. Keck, J. A. McAteer

Research output: Contribution to journalArticle

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Abstract

In renal cystic disease, fluid accumulation within cyst lumens might stretch cyst walls and in this way stimulate cell proliferation. To test this idea, the effects of mechanical stretch on Madin-Darby canine kidney cells grown as cysts in a hydrated collagen gel or as monolayers on collagen-coated Flexcell membranes were examined. The percentage of cells synthesizing DNA (labeling index) was determined by measuring bromodeoxyuridine incorporation and counting cell numbers. The distension of single cysts for 1 h by the intraluminal injection of saline failed to produce a significant increase in labeling index. The exposure of cysts for 2.5 h to 1 mM dibutyryl cAMP + 0.1 mM isobutylmethylxanthine led to a 37% increase in luminal surface area (due to stimulated fluid secretion) and a 30% increase in labeling index. The stretch (25%) of Madin-Darby canine kidney monolayers approximately doubled the labeling index between 12 and 24 h after starting the stretch. After 48 h, the cell population density was significantly increased (P < 0.001), from 41.9 ± 0.2 (SE; N = 12) to 48.2 ± 0.5 (N = 12) cells/10,000 μm2. The labeling index increased linearly with applied stretch, from 7.2 ± 0.3% (N = 36) with no stretch to 16.2 ± 1.0% (N = 6) with 30% stretch. Stretch had to be maintained for 8 h or more to produce an increase in labeling index at 18 h. No evidence was obtained for the release of a diffusible growth factor by stretched monolayers. The increase in labeling index induced by stretch was unaffected by 50 μM gadolinium, a stretch-activated channel blocker, but was abolished by 5 μg/mL cytochalasin B, an actin microfilament-disrupting agent. It was concluded that prolonged stretch stimulates renal epithelial cells to synthesize DNA. This supports the idea that increased wall tension in renal cysts may stimulate cell proliferation and, thereby, may contribute to cyst enlargement.

Original languageEnglish
Pages (from-to)1230-1241
Number of pages12
JournalJournal of the American Society of Nephrology
Volume6
Issue number4
StatePublished - 1995

Fingerprint

Cysts
Cell Proliferation
Kidney
Collagen
Cell Count
Cystic Kidney Diseases
Fluids and Secretions
Cytochalasin B
Madin Darby Canine Kidney Cells
DNA
Gadolinium
Bromodeoxyuridine
Population Density
In Vitro Techniques
Actin Cytoskeleton
Canidae
Intercellular Signaling Peptides and Proteins
Gels
Epithelial Cells
Injections

Keywords

  • Cell proliferation
  • Cultured renal epithelial cells
  • Madin-Darby canine kidney cells
  • Mechanical stretch
  • Renal cystic disease

ASJC Scopus subject areas

  • Nephrology

Cite this

Tanner, G. A., McQuillan, P. F., Maxwell, M. R., Keck, J. K., & McAteer, J. A. (1995). An in vitro test of the cell stretch-proliferation hypothesis of renal cyst enlargement. Journal of the American Society of Nephrology, 6(4), 1230-1241.

An in vitro test of the cell stretch-proliferation hypothesis of renal cyst enlargement. / Tanner, G. A.; McQuillan, P. F.; Maxwell, M. R.; Keck, J. K.; McAteer, J. A.

In: Journal of the American Society of Nephrology, Vol. 6, No. 4, 1995, p. 1230-1241.

Research output: Contribution to journalArticle

Tanner, GA, McQuillan, PF, Maxwell, MR, Keck, JK & McAteer, JA 1995, 'An in vitro test of the cell stretch-proliferation hypothesis of renal cyst enlargement', Journal of the American Society of Nephrology, vol. 6, no. 4, pp. 1230-1241.
Tanner, G. A. ; McQuillan, P. F. ; Maxwell, M. R. ; Keck, J. K. ; McAteer, J. A. / An in vitro test of the cell stretch-proliferation hypothesis of renal cyst enlargement. In: Journal of the American Society of Nephrology. 1995 ; Vol. 6, No. 4. pp. 1230-1241.
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