Dermal fibroblasts are one of the therapeutic targets for topical application of 1α,25-dihydroxyvitamin D3: The possible involvement of transforming growth factor-β induction

N. Oyama, K. Iwatsuki, M. Satoh, H. Akiba, F. Kaneko

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background Transforming growth factor (TGF) -β has been suggested to be an effective inhibitor for abnormal keratinocyte growth in psoriasis. As a majority of the secreted TGF-β are biologically latent complexes, activation is essential for TGF-β-mediated cellular responses in vitro and in vivo. I Objectives Here we report the response of the TGF-β regulation system to 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], an active vitamin D3 analogue Patients/methods We studied two types of fibroblasts derived from normal and psoriatic lesional skin, using an enzyme-linked immunosorbent assay and Northern blotting techniques. Proteins in Results 1,25(OH)23 caused a dose-dependent induction of latent and active TGF-β1 both cell cultures. The increases were significant over 72 h. but not within 48 h after stimulation. The time course of TGF-β1 mRNA expression showed a biphasic response consisting of early (≈1 h) and late phases (≈ 96 h) of induction. Concomitant increases of TGF-β2 and -β3, other mammalian isoforms, were observed in the 1,25(OH)2D3-treated cells, but the kinetics were all different. Coincubation with metabolic inhibitors, actinomycin D and cycloheximide, revealed that the early induction of TGF-β1 mRNA by 1,25(OH)2D3 is dependent on de novo RNA synthesis, but not on RNA stabilization or protein synthesis. It seems likely to be a transient and negligible response given the absence of TGF-β1 protein production. The late induction of TGF-β1 mRNA was partially I blocked by adding isoform-specific antibodies to TGF-β1, -β2 and -β3, indicating TGF-β auto -regulation. Despite these marked responses, there were no significant differences in the TGF-β expression between normal and psoriatic fibroblasts. I Conclusions These results suggest that antiproliferative and anti-inflammatory effects of 1,25(OH)2D3 on psoriatic lesional skin may be mediated, at least in part, by a complex TGF-β regulation in local dermal fibroblasts.

Original languageEnglish
Pages (from-to)1140-1148
Number of pages9
JournalBritish Journal of Dermatology
Volume143
Issue number6
DOIs
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Calcitriol
Transforming Growth Factors
Fibroblasts
Skin
Therapeutics
Messenger RNA
Protein Isoforms
RNA
Proteins
Cholecalciferol
Dactinomycin
Cycloheximide
Keratinocytes
Psoriasis
Northern Blotting

Keywords

  • Autoregulation
  • Dermal fibroblasts
  • Psoriasis
  • Transforming growth factor-β
  • Vitamin D

ASJC Scopus subject areas

  • Dermatology

Cite this

Dermal fibroblasts are one of the therapeutic targets for topical application of 1α,25-dihydroxyvitamin D3 : The possible involvement of transforming growth factor-β induction. / Oyama, N.; Iwatsuki, K.; Satoh, M.; Akiba, H.; Kaneko, F.

In: British Journal of Dermatology, Vol. 143, No. 6, 2000, p. 1140-1148.

Research output: Contribution to journalArticle

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abstract = "Background Transforming growth factor (TGF) -β has been suggested to be an effective inhibitor for abnormal keratinocyte growth in psoriasis. As a majority of the secreted TGF-β are biologically latent complexes, activation is essential for TGF-β-mediated cellular responses in vitro and in vivo. I Objectives Here we report the response of the TGF-β regulation system to 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], an active vitamin D3 analogue Patients/methods We studied two types of fibroblasts derived from normal and psoriatic lesional skin, using an enzyme-linked immunosorbent assay and Northern blotting techniques. Proteins in Results 1,25(OH)23 caused a dose-dependent induction of latent and active TGF-β1 both cell cultures. The increases were significant over 72 h. but not within 48 h after stimulation. The time course of TGF-β1 mRNA expression showed a biphasic response consisting of early (≈1 h) and late phases (≈ 96 h) of induction. Concomitant increases of TGF-β2 and -β3, other mammalian isoforms, were observed in the 1,25(OH)2D3-treated cells, but the kinetics were all different. Coincubation with metabolic inhibitors, actinomycin D and cycloheximide, revealed that the early induction of TGF-β1 mRNA by 1,25(OH)2D3 is dependent on de novo RNA synthesis, but not on RNA stabilization or protein synthesis. It seems likely to be a transient and negligible response given the absence of TGF-β1 protein production. The late induction of TGF-β1 mRNA was partially I blocked by adding isoform-specific antibodies to TGF-β1, -β2 and -β3, indicating TGF-β auto -regulation. Despite these marked responses, there were no significant differences in the TGF-β expression between normal and psoriatic fibroblasts. I Conclusions These results suggest that antiproliferative and anti-inflammatory effects of 1,25(OH)2D3 on psoriatic lesional skin may be mediated, at least in part, by a complex TGF-β regulation in local dermal fibroblasts.",
keywords = "Autoregulation, Dermal fibroblasts, Psoriasis, Transforming growth factor-β, Vitamin D",
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T1 - Dermal fibroblasts are one of the therapeutic targets for topical application of 1α,25-dihydroxyvitamin D3

T2 - The possible involvement of transforming growth factor-β induction

AU - Oyama, N.

AU - Iwatsuki, K.

AU - Satoh, M.

AU - Akiba, H.

AU - Kaneko, F.

PY - 2000

Y1 - 2000

N2 - Background Transforming growth factor (TGF) -β has been suggested to be an effective inhibitor for abnormal keratinocyte growth in psoriasis. As a majority of the secreted TGF-β are biologically latent complexes, activation is essential for TGF-β-mediated cellular responses in vitro and in vivo. I Objectives Here we report the response of the TGF-β regulation system to 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], an active vitamin D3 analogue Patients/methods We studied two types of fibroblasts derived from normal and psoriatic lesional skin, using an enzyme-linked immunosorbent assay and Northern blotting techniques. Proteins in Results 1,25(OH)23 caused a dose-dependent induction of latent and active TGF-β1 both cell cultures. The increases were significant over 72 h. but not within 48 h after stimulation. The time course of TGF-β1 mRNA expression showed a biphasic response consisting of early (≈1 h) and late phases (≈ 96 h) of induction. Concomitant increases of TGF-β2 and -β3, other mammalian isoforms, were observed in the 1,25(OH)2D3-treated cells, but the kinetics were all different. Coincubation with metabolic inhibitors, actinomycin D and cycloheximide, revealed that the early induction of TGF-β1 mRNA by 1,25(OH)2D3 is dependent on de novo RNA synthesis, but not on RNA stabilization or protein synthesis. It seems likely to be a transient and negligible response given the absence of TGF-β1 protein production. The late induction of TGF-β1 mRNA was partially I blocked by adding isoform-specific antibodies to TGF-β1, -β2 and -β3, indicating TGF-β auto -regulation. Despite these marked responses, there were no significant differences in the TGF-β expression between normal and psoriatic fibroblasts. I Conclusions These results suggest that antiproliferative and anti-inflammatory effects of 1,25(OH)2D3 on psoriatic lesional skin may be mediated, at least in part, by a complex TGF-β regulation in local dermal fibroblasts.

AB - Background Transforming growth factor (TGF) -β has been suggested to be an effective inhibitor for abnormal keratinocyte growth in psoriasis. As a majority of the secreted TGF-β are biologically latent complexes, activation is essential for TGF-β-mediated cellular responses in vitro and in vivo. I Objectives Here we report the response of the TGF-β regulation system to 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], an active vitamin D3 analogue Patients/methods We studied two types of fibroblasts derived from normal and psoriatic lesional skin, using an enzyme-linked immunosorbent assay and Northern blotting techniques. Proteins in Results 1,25(OH)23 caused a dose-dependent induction of latent and active TGF-β1 both cell cultures. The increases were significant over 72 h. but not within 48 h after stimulation. The time course of TGF-β1 mRNA expression showed a biphasic response consisting of early (≈1 h) and late phases (≈ 96 h) of induction. Concomitant increases of TGF-β2 and -β3, other mammalian isoforms, were observed in the 1,25(OH)2D3-treated cells, but the kinetics were all different. Coincubation with metabolic inhibitors, actinomycin D and cycloheximide, revealed that the early induction of TGF-β1 mRNA by 1,25(OH)2D3 is dependent on de novo RNA synthesis, but not on RNA stabilization or protein synthesis. It seems likely to be a transient and negligible response given the absence of TGF-β1 protein production. The late induction of TGF-β1 mRNA was partially I blocked by adding isoform-specific antibodies to TGF-β1, -β2 and -β3, indicating TGF-β auto -regulation. Despite these marked responses, there were no significant differences in the TGF-β expression between normal and psoriatic fibroblasts. I Conclusions These results suggest that antiproliferative and anti-inflammatory effects of 1,25(OH)2D3 on psoriatic lesional skin may be mediated, at least in part, by a complex TGF-β regulation in local dermal fibroblasts.

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