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Proliferation and differentiation of keratinocytes are normally well balanced, but this balance can be perturbed in wound healing and is dysregulated in pathological conditions such as atopic dermatitis. Epithelial–mesenchymal interaction affects this event via the cross-talk of cytokines and growth factors. Periostin, a matricellular protein, has an important role during reepithelialization in wound healing and is critical for hyperproliferation of keratinocytes in atopic dermatitis. Here we investigated how periostin regulates proliferation and differentiation of keratinocytes in the epithelial–mesenchymal interactions using a three-dimensional organotypic air–liquid interface coculture system. The release of IL-1α from keratinocytes and subsequent IL-6 production from fibroblasts were critical for keratinocyte proliferation and differentiation. Periostin secreted from fibroblasts was required for IL-1α-induced IL-6 production and enhanced IL-6 production by activation of the NF-κB pathway synergistically with IL-1α. Thus, the combination of an autocrine loop of periostin and a paracrine loop composed of IL-1α and IL-6 regulates keratinocyte proliferation and differentiation in the epithelial–mesenchymal interactions, and periostin tunes the magnitude of keratinocyte proliferation and differentiation by interacting with the paracrine IL-1α/IL-6 loop.

Cutaneous wound repair is a highly ordered and well-coordinated process involving various cell lineages and many molecular effectors. Cell-matrix interactions through integrin molecules provide key signals important for wound repair. Periostin is a matricellular protein that may provide signals important during tissue development and remodelling by interacting with several integrin molecules, via the phosphatidylinositol 3-kinase/Akt and MAP kinase pathways. In this study, we examined the role of periostin in the process of cutaneous wound repair using periostin-deficient mice and by analysing the effects of periostin on dermal fibroblasts. We first determined the expression profile and localization of periostin in a well-characterized wound repair model mice. Periostin was robustly deposited in the granulation tissues beneath the extended epidermal wound edges and at the dermal-epidermal junctions in wounded mice. Moreover, periostin-deficient mice exhibited delayed in vivo wound repair, which could be improved by direct administration of exogenous periostin. In vitro analyses revealed that loss of periostin impaired proliferation and migration of dermal fibroblasts, but exogenous supplementation or enforced periostin expression enhanced their proliferation. Combined, these results demonstrate that periostin accelerates the process of cutaneous wound repair by activating fibroblasts.

70歳，男性。初診の4ヵ月前より背部にそう痒を伴う紅斑が出現した。膝関節，手背にも紅斑が拡大し，下肢の筋力低下も伴うようになった。臨床所見及び病理組織学的所見より皮膚筋炎と診断した。初診時血液検査にて汎血球減少と異型リンパ球を認めたため，造血器悪性腫瘍を疑い骨髄穿刺を施行し，急性骨髄性白血病と診断した。皮膚筋炎に悪性腫瘍を合併することが多いことは知られているが，急性骨髄性白血病を合併する症例は非常に稀であり，国内外併せて自験例を含め3例のみであった。悪性腫瘍を合併した皮膚筋炎について若干の考察を加えた。

Cutaneous wound repair is a highly ordered and well-coordinated process involving various cell lineages and many molecular effectors. Cell-matrix interactions through integrin molecules provide key signals important for wound repair. Periostin is a matricellular protein that may provide signals important during tissue development and remodelling by interacting with several integrin molecules, via the phosphatidylinositol 3-kinase/Akt and MAP kinase pathways. In this study, we examined the role of periostin in the process of cutaneous wound repair using periostin-deficient mice and by analysing the effects of periostin on dermal fibroblasts. We first determined the expression profile and localization of periostin in a well-characterized wound repair model mice. Periostin was robustly deposited in the granulation tissues beneath the extended epidermal wound edges and at the dermal-epidermal junctions in wounded mice. Moreover, periostin-deficient mice exhibited delayed in vivo wound repair, which could be improved by direct administration of exogenous periostin. In vitro analyses revealed that loss of periostin impaired proliferation and migration of dermal fibroblasts, but exogenous supplementation or enforced periostin expression enhanced their proliferation. Combined, these results demonstrate that periostin accelerates the process of cutaneous wound repair by activating fibroblasts.