Retinoic acid stimulation of human dermal fibroblast proliferation is dependent on suboptimal extracellular Ca2+ concentration

James Varani, Jay R. Shayevitz, Debra Perry, Raj S. Mitra, Brian J. Nickoloff, John J. Voorhees

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Human dermal fibrobtasts failed to proliferate when cultured in medium containing 0.15 mmol/ l (millimolar) Ca2+ (keratinocyte growth medium [KGM]) but did when the external Ca2+ concentration was raised to 1.4 mmol/l. All-trans retinoic acid (retinoic acid) stimulated proliferation in KGM but did not further stimulate growth in Ca2+-supplemented KGM. The ability of retinoic acid to stimulate proliferation was inhibited in KGM pre-pared without Ca2+ or prepared with 0.03 mmol/l Ca2+ and in KGM treated with 1 mmol/l ethylene-glycol-bis-(β-aminoethyl ether)N,N′-tetra acetic acid. Using 45Ca2+ to measure Ca2+ influx and efflux, it was found that retinoic acid minimally increased Ca2+ uptake into flbroblasts. In contrast, retinoic acid treatment of fibroblasts that had been pre-equilibrated for 1 day with 45Ca2+ inhibited release of intracellular Ca2+ into the extracellular fluid. Retinoic acid also stimulated 35S-methionine incorporation into trichloroacetic acid-precipitable material but in contrast to its effect on proliferation, stimulation of 35S-methionine incorporation occurred in both high-Ca2+ and low-Ca2+ medium. These data indicate that retinoic acid stimulation of proliferation, but not protein synthesis, is dependent on the concentration of Ca2+ in the extracellular environment.

Original languageEnglish (US)
Pages (from-to)1275-1281
Number of pages7
JournalAmerican Journal of Pathology
Volume136
Issue number6
StatePublished - Jun 1990
Externally publishedYes

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Tretinoin
Fibroblasts
Keratinocytes
Skin
Growth
Methionine
Trichloroacetic Acid
Ethylene Glycol
Extracellular Fluid
Acetic Acid
Ether
Contrast Media
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Varani, J., Shayevitz, J. R., Perry, D., Mitra, R. S., Nickoloff, B. J., & Voorhees, J. J. (1990). Retinoic acid stimulation of human dermal fibroblast proliferation is dependent on suboptimal extracellular Ca2+ concentration. American Journal of Pathology, 136(6), 1275-1281.

Retinoic acid stimulation of human dermal fibroblast proliferation is dependent on suboptimal extracellular Ca2+ concentration. / Varani, James; Shayevitz, Jay R.; Perry, Debra; Mitra, Raj S.; Nickoloff, Brian J.; Voorhees, John J.

In: American Journal of Pathology, Vol. 136, No. 6, 06.1990, p. 1275-1281.

Research output: Contribution to journalArticle

Varani, J, Shayevitz, JR, Perry, D, Mitra, RS, Nickoloff, BJ & Voorhees, JJ 1990, 'Retinoic acid stimulation of human dermal fibroblast proliferation is dependent on suboptimal extracellular Ca2+ concentration', American Journal of Pathology, vol. 136, no. 6, pp. 1275-1281.
Varani, James ; Shayevitz, Jay R. ; Perry, Debra ; Mitra, Raj S. ; Nickoloff, Brian J. ; Voorhees, John J. / Retinoic acid stimulation of human dermal fibroblast proliferation is dependent on suboptimal extracellular Ca2+ concentration. In: American Journal of Pathology. 1990 ; Vol. 136, No. 6. pp. 1275-1281.
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