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Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice.

Michalik L, Desvergne B, Tan NS, Basu-Modak S, Escher P, Rieusset J, Peters JM, Kaya G, Gonzalez FJ, Zakany J, Metzger D, Chambon P, Duboule D, Wahli W - J. Cell Biol. (2001)

Bottom Line: Interestingly, PPARalpha and beta expression is reactivated in the adult epidermis after various stimuli, resulting in keratinocyte proliferation and differentiation such as tetradecanoylphorbol acetate topical application, hair plucking, or skin wound healing.PPARalpha is mainly involved in the early inflammation phase of the healing, whereas PPARbeta is implicated in the control of keratinocyte proliferation.In addition and very interestingly, PPARbeta mutant primary keratinocytes show impaired adhesion and migration properties.

View Article: PubMed Central - PubMed

Affiliation: Institut de Biologie Animale, Université de Lausanne, Bâtiment de Biologie, CH-1015 Lausanne, Switzerland.

ABSTRACT
We show here that the alpha, beta, and gamma isotypes of peroxisome proliferator-activated receptor (PPAR) are expressed in the mouse epidermis during fetal development and that they disappear progressively from the interfollicular epithelium after birth. Interestingly, PPARalpha and beta expression is reactivated in the adult epidermis after various stimuli, resulting in keratinocyte proliferation and differentiation such as tetradecanoylphorbol acetate topical application, hair plucking, or skin wound healing. Using PPARalpha, beta, and gamma mutant mice, we demonstrate that PPARalpha and beta are important for the rapid epithelialization of a skin wound and that each of them plays a specific role in this process. PPARalpha is mainly involved in the early inflammation phase of the healing, whereas PPARbeta is implicated in the control of keratinocyte proliferation. In addition and very interestingly, PPARbeta mutant primary keratinocytes show impaired adhesion and migration properties. Thus, the findings presented here reveal unpredicted roles for PPARalpha and beta in adult mouse epidermal repair.

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Related in: MedlinePlus

Differential expression of PPAR in adult mouse epidermis during cutaneous wound closure. Cryosections of mouse skin from day 1 to 10 (+1 to +10) after the excision of a full thickness dorsal skin biopsy were hematoxilin/eosin stained (HE) or hybridized with specific antisense digoxygenin-labeled riboprobes (PPARα, β, or γ). Arrows indicate the epidermis/dermis interface. A similar pattern of expression was observed for each time point in six different mice from independent litters. Bar, 80 μm.
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fig5: Differential expression of PPAR in adult mouse epidermis during cutaneous wound closure. Cryosections of mouse skin from day 1 to 10 (+1 to +10) after the excision of a full thickness dorsal skin biopsy were hematoxilin/eosin stained (HE) or hybridized with specific antisense digoxygenin-labeled riboprobes (PPARα, β, or γ). Arrows indicate the epidermis/dermis interface. A similar pattern of expression was observed for each time point in six different mice from independent litters. Bar, 80 μm.

Mentions: A half centimeter square, full thickness skin biopsy was excised from the back of adult mice, and PPAR expression was assessed by in situ hybridization at several time points after the injury at the site of the wound (Fig. 5) . In situ hybridization revealed that PPARα and PPARβ are both upregulated in the epidermis of the wound edges, compared with a normal adult epidermis where they cannot be detected. PPARβ reactivation was detected as early as 24 h after the injury. Furthermore, it remained expressed in the epidermis of the wound edges and in the neoepithelium during the whole healing process. After closure of the wound, PPARβ was downregulated and it became undetectable 20 d after injury. In contrast, PPARα expression was observed during a short period of time only, ∼3 d after the injury, and was not observed thereafter. The third isotype, PPARγ, was hardly detectable, which suggests modest or no implication of this isotype in the skin wound–healing process.


Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice.

Michalik L, Desvergne B, Tan NS, Basu-Modak S, Escher P, Rieusset J, Peters JM, Kaya G, Gonzalez FJ, Zakany J, Metzger D, Chambon P, Duboule D, Wahli W - J. Cell Biol. (2001)

Differential expression of PPAR in adult mouse epidermis during cutaneous wound closure. Cryosections of mouse skin from day 1 to 10 (+1 to +10) after the excision of a full thickness dorsal skin biopsy were hematoxilin/eosin stained (HE) or hybridized with specific antisense digoxygenin-labeled riboprobes (PPARα, β, or γ). Arrows indicate the epidermis/dermis interface. A similar pattern of expression was observed for each time point in six different mice from independent litters. Bar, 80 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196455&req=5

fig5: Differential expression of PPAR in adult mouse epidermis during cutaneous wound closure. Cryosections of mouse skin from day 1 to 10 (+1 to +10) after the excision of a full thickness dorsal skin biopsy were hematoxilin/eosin stained (HE) or hybridized with specific antisense digoxygenin-labeled riboprobes (PPARα, β, or γ). Arrows indicate the epidermis/dermis interface. A similar pattern of expression was observed for each time point in six different mice from independent litters. Bar, 80 μm.
Mentions: A half centimeter square, full thickness skin biopsy was excised from the back of adult mice, and PPAR expression was assessed by in situ hybridization at several time points after the injury at the site of the wound (Fig. 5) . In situ hybridization revealed that PPARα and PPARβ are both upregulated in the epidermis of the wound edges, compared with a normal adult epidermis where they cannot be detected. PPARβ reactivation was detected as early as 24 h after the injury. Furthermore, it remained expressed in the epidermis of the wound edges and in the neoepithelium during the whole healing process. After closure of the wound, PPARβ was downregulated and it became undetectable 20 d after injury. In contrast, PPARα expression was observed during a short period of time only, ∼3 d after the injury, and was not observed thereafter. The third isotype, PPARγ, was hardly detectable, which suggests modest or no implication of this isotype in the skin wound–healing process.

Bottom Line: Interestingly, PPARalpha and beta expression is reactivated in the adult epidermis after various stimuli, resulting in keratinocyte proliferation and differentiation such as tetradecanoylphorbol acetate topical application, hair plucking, or skin wound healing.PPARalpha is mainly involved in the early inflammation phase of the healing, whereas PPARbeta is implicated in the control of keratinocyte proliferation.In addition and very interestingly, PPARbeta mutant primary keratinocytes show impaired adhesion and migration properties.

View Article: PubMed Central - PubMed

Affiliation: Institut de Biologie Animale, Université de Lausanne, Bâtiment de Biologie, CH-1015 Lausanne, Switzerland.

ABSTRACT
We show here that the alpha, beta, and gamma isotypes of peroxisome proliferator-activated receptor (PPAR) are expressed in the mouse epidermis during fetal development and that they disappear progressively from the interfollicular epithelium after birth. Interestingly, PPARalpha and beta expression is reactivated in the adult epidermis after various stimuli, resulting in keratinocyte proliferation and differentiation such as tetradecanoylphorbol acetate topical application, hair plucking, or skin wound healing. Using PPARalpha, beta, and gamma mutant mice, we demonstrate that PPARalpha and beta are important for the rapid epithelialization of a skin wound and that each of them plays a specific role in this process. PPARalpha is mainly involved in the early inflammation phase of the healing, whereas PPARbeta is implicated in the control of keratinocyte proliferation. In addition and very interestingly, PPARbeta mutant primary keratinocytes show impaired adhesion and migration properties. Thus, the findings presented here reveal unpredicted roles for PPARalpha and beta in adult mouse epidermal repair.

Show MeSH
Related in: MedlinePlus