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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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Normal keratinocyte-terminal differentiation in PPARβ1/− skin. (a–f) PPARβ+/+ fetal (E18.5) (a–c) or adult (d–f) dorsal epidermis, hematoxilin/eosin staining (HE) (a and d), and after involucrin (b and e) or loricrin (c and f) immunostaining. (g–l) PPARβ+/− fetal (E18.5) (g–i) or adult (j–l) dorsal epidermis, hematoxilin/eosin staining (HE) (g and j), and after involucrin (h and k) or loricrin (i and l) immunostaining. Arrows indicate the epidermis/dermis interface. Bars, 40 μm.
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fig4: Normal keratinocyte-terminal differentiation in PPARβ1/− skin. (a–f) PPARβ+/+ fetal (E18.5) (a–c) or adult (d–f) dorsal epidermis, hematoxilin/eosin staining (HE) (a and d), and after involucrin (b and e) or loricrin (c and f) immunostaining. (g–l) PPARβ+/− fetal (E18.5) (g–i) or adult (j–l) dorsal epidermis, hematoxilin/eosin staining (HE) (g and j), and after involucrin (h and k) or loricrin (i and l) immunostaining. Arrows indicate the epidermis/dermis interface. Bars, 40 μm.

Mentions: Because PPARβ is expressed in the epidermis during fetal and postnatal development (Fig. 1), and because of its involvement in the control of keratinocyte proliferation (Fig. 3), the question was raised whether the differentiation process would also be affected in the epidermis of PPARβ mutant mice. To address this question, the skin morphology and the pattern of expression of several keratinocyte differentiation markers (keratins 14 and 10, loricrin, involucrin) were analyzed in the epidermis of PPARβ mutant mice from day 14.5 of gestation until adulthood. As shown after histological staining, the PPARβ mutant mice show normal skin architecture, both during fetal development (embryonic day 14.5 and 16.5, data not shown; embryonic day 18.5, Fig. 4) and at the adult stage (Fig. 4). Immunofluorescent labelings revealed that the pattern and the time course of expression of the above mentioned differentiation markers was similar in the PPARβ mutant and the wild-type control epidermis (Fig. 4 and data not shown).


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)

Normal keratinocyte-terminal differentiation in PPARβ1/− skin. (a–f) PPARβ+/+ fetal (E18.5) (a–c) or adult (d–f) dorsal epidermis, hematoxilin/eosin staining (HE) (a and d), and after involucrin (b and e) or loricrin (c and f) immunostaining. (g–l) PPARβ+/− fetal (E18.5) (g–i) or adult (j–l) dorsal epidermis, hematoxilin/eosin staining (HE) (g and j), and after involucrin (h and k) or loricrin (i and l) immunostaining. Arrows indicate the epidermis/dermis interface. Bars, 40 μm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196455&req=5

fig4: Normal keratinocyte-terminal differentiation in PPARβ1/− skin. (a–f) PPARβ+/+ fetal (E18.5) (a–c) or adult (d–f) dorsal epidermis, hematoxilin/eosin staining (HE) (a and d), and after involucrin (b and e) or loricrin (c and f) immunostaining. (g–l) PPARβ+/− fetal (E18.5) (g–i) or adult (j–l) dorsal epidermis, hematoxilin/eosin staining (HE) (g and j), and after involucrin (h and k) or loricrin (i and l) immunostaining. Arrows indicate the epidermis/dermis interface. Bars, 40 μm.
Mentions: Because PPARβ is expressed in the epidermis during fetal and postnatal development (Fig. 1), and because of its involvement in the control of keratinocyte proliferation (Fig. 3), the question was raised whether the differentiation process would also be affected in the epidermis of PPARβ mutant mice. To address this question, the skin morphology and the pattern of expression of several keratinocyte differentiation markers (keratins 14 and 10, loricrin, involucrin) were analyzed in the epidermis of PPARβ mutant mice from day 14.5 of gestation until adulthood. As shown after histological staining, the PPARβ mutant mice show normal skin architecture, both during fetal development (embryonic day 14.5 and 16.5, data not shown; embryonic day 18.5, Fig. 4) and at the adult stage (Fig. 4). Immunofluorescent labelings revealed that the pattern and the time course of expression of the above mentioned differentiation markers was similar in the PPARβ mutant and the wild-type control epidermis (Fig. 4 and data not shown).

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