Possibilities for the Therapeutic Control of Fibrosis

Ci, Levene

doi:10.1111/j.1365-2133.1985.tb04866.x

Br J Dermatol

1985

DOI: 10.1111/j.1365-2133.1985.tb04866.x

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Possibilities for the Therapeutic Control of Fibrosis

Levene Ci

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1985

1991

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Cited by 4 publications

References 45 publications

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Cell-mediated contraction of collagen lattices in serum-free medium: Effect of serum and nonserum factors

Anderson¹,

Ruben²,

Fuller³

1990

In Vitro Cell Dev Biol

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This study was conducted to identify a defined, serum-free culture medium that supports cell dependent contraction of a collagen lattice. Collagen lattices were found to contract in cultures containing human foreskin fibroblasts (HFF) or rabbit aortic smooth muscle (RASM) cells incubated in serum-free medium. HFF and RASM cells required different supplements to contract the collagen gels. HFF cultured in Dulbecco's modified Eagle's (DME) medium supplemented with bovine serum albumin (BSA) and either endothelial cell growth supplement (EnGS), insulin (In), or platelet derived growth factor (PDGF) supported collagen lattice contraction. Replacement of BSA with casein without the addition of other supplements improved contraction. In contrast, RASM cells supplemented with BSA, EnGS, In, and PDGF were able to contract collagen gels only minimally. Similar to HFF, RASM cells cultured in DME medium supplemented with casein, but without the addition of other supplements, contracted collagen lattices. HFF-mediated collagen contraction was inhibited by prostaglandins E1 or E2, fibronectin, or ascorbic acid. The reported serum-free model provides a useful in vitro method to investigate the role of serum and nonserum factors regulating cell mediated-contraction of insoluble collagen fibrils.

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Cell-mediated contraction of collagen lattices in serum-free medium: Effect of serum and nonserum factors

Anderson¹,

Ruben²,

Fuller³

1990

In Vitro Cell Dev Biol

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Toxicity of the anthraquinone glycoside P-1894B for human skin fibroblasts

Priestley¹

1987

Br J Dermatol

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P-1894B inhibits prolyl hydroxylase in vitro and has been proposed as a topical treatment for dermal fibrosis. The drug had similar effects on two fibroblast lines from normal human skin and one line from a patient with lichen sclerosus et atrophicus. Exposure of logarithmically-growing cell monolayers for 72 h caused dose-dependent inhibition of proliferation at 0.05-0.5 microgram/ml but time-dependent cell death at 1-50 micrograms/ml. The epithelial cell line NCTC 2544 gave a similar result. Collagen lattices containing normal fibroblasts contracted more slowly in the presence of the drug at 0.1-0.5 microgram/ml, but this was clearly related to loss of viability. Collagen synthesis by monolayer cultures was unaffected at 0.05 and 0.1 microgram/ml P-1894B in one line of normal fibroblasts, but was reduced by 40% and 15%, respectively, in the other. The concentrations of P-1894B reported to be active against prolyl hydroxylase are therefore lethal to cultured skin cells. Although the effective use of dithranol as a topical anti-psoriatic agent, despite its cytotoxicity in vitro, is encouraging for P-1894B, further toxicological studies are imperative.

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The metabolism of fibroblasts from normal and fibrotic skin is inhibited by minoxidil in vitro

1991

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The effects of minoxidil in vitro were studied using fibroblasts grown from the lesional skin of patients with lichen sclerosus et atrophicus, morphoea and from the skin of normal individuals. The proliferation of all fibroblast lines over 3 days was inhibited in proportion to the concentration of minoxidil, being 20% or less of controls at 1 mM, where cell viability was only marginally reduced (84 +/- 2% vs. 88 +/- 2% (SEM) in controls). At 5 mM there was usually a net loss of cells and only 72% of those remaining were viable. In contrast, minoxidil at 0.1-1 mM stimulated the proliferation of foreskin keratinocytes by up to 130%. Contraction of collagen lattices containing the three types of fibroblasts was inhibited by 22-26% with 1 mM minoxidil after 5 days and by 50-94% with 5 mM. Secretion of glycosaminoglycans by normal fibroblasts showed concentration-dependent reduction, being 25 +/- 6% of that of untreated cultures with 1 mM minoxidil. These findings show that minoxidil has a range of inhibitory effects on both normal and abnormal skin fibroblasts in vitro, which contrast with its stimulation of skin epithelial cells, and support suggestions that it may provide a useful topical treatment for keloids and other fibroses.

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Possibilities for the Therapeutic Control of Fibrosis

Cited by 4 publications

References 45 publications

Cell-mediated contraction of collagen lattices in serum-free medium: Effect of serum and nonserum factors

Cell-mediated contraction of collagen lattices in serum-free medium: Effect of serum and nonserum factors

Toxicity of the anthraquinone glycoside P-1894B for human skin fibroblasts

The metabolism of fibroblasts from normal and fibrotic skin is inhibited by minoxidil in vitro

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