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REDD1 functions at the crossroads between the therapeutic and adverse effects of topical glucocorticoids.

Baida G, Bhalla P, Kirsanov K, Lesovaya E, Yakubovskaya M, Yuen K, Guo S, Lavker RM, Readhead B, Dudley JT, Budunova I - EMBO Mol Med (2014)

Bottom Line: Moreover, REDD1 knockdown resulted in similar consequences in organotypic raft cultures of primary human keratinocytes.Importantly, the lack of REDD1 did not diminish the anti-inflammatory effects of glucocorticoids in preclinical model.Our findings suggest that combining steroids with REDD1 inhibitors may yield a novel, safer glucocorticoid-based therapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Northwestern University, Chicago, IL, USA.

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Related in: MedlinePlus

REDD1 KO mice are resistant to glucocorticoid-induced skin atrophyREDD1 KO and isogenic wild-type B6x129 mice were treated with acetone (vehicle control) or FA (2 μg/animal) every 72 h for 2 weeks.A, B H&E staining (A) and Masson's trichrome staining: Dermis/collagen fibers are blue, muscle is red, nuclei are dark red, and cytoplasm is red/pink (B). Arrows point to epidermis and brackets indicate subcutaneous adipose (A) and dermis (D). Scale bars are 20 μm.C, D Morphometric analysis of epidermal thickness and dermal cellularity as described in Materials and Methods. Changes in epidermal thickness (C) are presented as % to wild-type control epidermis. Changes in dermal cellularity (D) are presented as % to corresponding control skin. The means ± SD were calculated for three individual skin samples in one representative experiment (30 measurements/condition) out of two experiments. Statistical analysis for differences between treatment and control and between control wild-type and REDD1 KO epidermal thickness was done by the unpaired two-tailed t-test.
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fig03: REDD1 KO mice are resistant to glucocorticoid-induced skin atrophyREDD1 KO and isogenic wild-type B6x129 mice were treated with acetone (vehicle control) or FA (2 μg/animal) every 72 h for 2 weeks.A, B H&E staining (A) and Masson's trichrome staining: Dermis/collagen fibers are blue, muscle is red, nuclei are dark red, and cytoplasm is red/pink (B). Arrows point to epidermis and brackets indicate subcutaneous adipose (A) and dermis (D). Scale bars are 20 μm.C, D Morphometric analysis of epidermal thickness and dermal cellularity as described in Materials and Methods. Changes in epidermal thickness (C) are presented as % to wild-type control epidermis. Changes in dermal cellularity (D) are presented as % to corresponding control skin. The means ± SD were calculated for three individual skin samples in one representative experiment (30 measurements/condition) out of two experiments. Statistical analysis for differences between treatment and control and between control wild-type and REDD1 KO epidermal thickness was done by the unpaired two-tailed t-test.

Mentions: To assess the causative role of REDD1 in therapeutic and side effects of glucocorticoids in the skin, we compared REDD1 KO mice (Brafman et al, 2004) with isogenic controls (B6x129). REDD1 KO mice displayed mild epidermal hyperplasia and slightly increased keratinocyte proliferation (Fig3C and data not shown). There were no significant changes in early and medium/late differentiation markers including keratins K5, K10, loricrin, and involucrin (Supplementary Fig S2).


REDD1 functions at the crossroads between the therapeutic and adverse effects of topical glucocorticoids.

Baida G, Bhalla P, Kirsanov K, Lesovaya E, Yakubovskaya M, Yuen K, Guo S, Lavker RM, Readhead B, Dudley JT, Budunova I - EMBO Mol Med (2014)

REDD1 KO mice are resistant to glucocorticoid-induced skin atrophyREDD1 KO and isogenic wild-type B6x129 mice were treated with acetone (vehicle control) or FA (2 μg/animal) every 72 h for 2 weeks.A, B H&E staining (A) and Masson's trichrome staining: Dermis/collagen fibers are blue, muscle is red, nuclei are dark red, and cytoplasm is red/pink (B). Arrows point to epidermis and brackets indicate subcutaneous adipose (A) and dermis (D). Scale bars are 20 μm.C, D Morphometric analysis of epidermal thickness and dermal cellularity as described in Materials and Methods. Changes in epidermal thickness (C) are presented as % to wild-type control epidermis. Changes in dermal cellularity (D) are presented as % to corresponding control skin. The means ± SD were calculated for three individual skin samples in one representative experiment (30 measurements/condition) out of two experiments. Statistical analysis for differences between treatment and control and between control wild-type and REDD1 KO epidermal thickness was done by the unpaired two-tailed t-test.
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Related In: Results  -  Collection

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fig03: REDD1 KO mice are resistant to glucocorticoid-induced skin atrophyREDD1 KO and isogenic wild-type B6x129 mice were treated with acetone (vehicle control) or FA (2 μg/animal) every 72 h for 2 weeks.A, B H&E staining (A) and Masson's trichrome staining: Dermis/collagen fibers are blue, muscle is red, nuclei are dark red, and cytoplasm is red/pink (B). Arrows point to epidermis and brackets indicate subcutaneous adipose (A) and dermis (D). Scale bars are 20 μm.C, D Morphometric analysis of epidermal thickness and dermal cellularity as described in Materials and Methods. Changes in epidermal thickness (C) are presented as % to wild-type control epidermis. Changes in dermal cellularity (D) are presented as % to corresponding control skin. The means ± SD were calculated for three individual skin samples in one representative experiment (30 measurements/condition) out of two experiments. Statistical analysis for differences between treatment and control and between control wild-type and REDD1 KO epidermal thickness was done by the unpaired two-tailed t-test.
Mentions: To assess the causative role of REDD1 in therapeutic and side effects of glucocorticoids in the skin, we compared REDD1 KO mice (Brafman et al, 2004) with isogenic controls (B6x129). REDD1 KO mice displayed mild epidermal hyperplasia and slightly increased keratinocyte proliferation (Fig3C and data not shown). There were no significant changes in early and medium/late differentiation markers including keratins K5, K10, loricrin, and involucrin (Supplementary Fig S2).

Bottom Line: Moreover, REDD1 knockdown resulted in similar consequences in organotypic raft cultures of primary human keratinocytes.Importantly, the lack of REDD1 did not diminish the anti-inflammatory effects of glucocorticoids in preclinical model.Our findings suggest that combining steroids with REDD1 inhibitors may yield a novel, safer glucocorticoid-based therapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Northwestern University, Chicago, IL, USA.

Show MeSH
Related in: MedlinePlus