Periostin localizes to cells in normal skin, but is associated with the extracellular matrix during wound repair

Abstract

Epidermal tissue repair represents a complex series of temporal and dynamic events resulting in wound closure. Matricellular proteins, not normally expressed in quiescent adult tissues, play a pivotal role in wound repair and associated extracellular matrix remodeling by modulating the adhesion, migration, intracellular signaling, and gene expression of inflammatory cells, pericytes, fibroblasts and keratinocytes. Several matricellular proteins show temporal expression during dermal wound repair, but the expression pattern of the recently identified matricellular protein, periostin, has not yet been characterized. The primary aim of this study was to assess whether periostin protein is present in healthy human skin or in pathological remodeling (Nevus). The second aim was to determine if periostin is expressed during dermal wound repair. Using immunohistochemistry, periostin reactivity was detected in the keratinocytes, basal lamina, and dermal fibroblasts in healthy human skin. In pathological nevus samples, periostin was present in the extracellular matrix. In excisional wounds in mice, periostin protein was first detected in the granulation tissue at day 3, with levels peaking at day 7. Periostin protein co-localized with α-smooth muscle actin-positive cells and keratinocytes, but not CD68 positive inflammatory cells. We conclude that periostin is normally expressed at the cellular level in human and murine skin, but additionally becomes extracellular during tissue remodeling. Periostin may represent a new therapeutic target for modulating the wound repair process.

Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair

“…Additionally, induction of periostin expression has been described following acute injury to numerous tissues (Goetsch et al, 2003;Li et al, 2006;Lindner et al, 2005;Nakazawa et al, 2004), including skin (Jackson-Boeters et al, 2009; Lindner et al, 2005;Zhou et al, 2010), where expression peaks at 7-8 days and returns to basal levels by 4 weeks. Our previous reports on skin repair show that periostin expression is absent during inflammation, but instead corresponds with the proliferative and remodeling phases of repair (Jackson-Boeters et al, 2009;Zhou et al, 2010), suggesting a role for periostin during these later phases.…”

Functional significance of periostin in excisional skin repair

“…Following acute injury periostin has been shown to be potently upregulated in bone, 4 heart, 5,6 vasculature 7,8 and muscle. 9 Beginning with Lindner and colleagues in 2005, 8 and more recently from our lab, 10,11 periostin has also been implicated in skin development and repair. In all described remodeling situations, periostin upregulation follows a highly conserved pattern (beginning at day 3, peaking around day 7 and eventually returning to baseline by 4 weeks), suggesting a consistent role for periostin in tissue repair process.…”

“…Moreover, all studies show a significant peak in periostin expression at day 7, confirming our initial finding. 10 In normal skin periostin is localized at the dermal-epidermal junction (DEJ) and in hair follicles. Following excisional wounding in Postn +/+ mice, periostin is predominantly expressed in the granulation tissue and in neighboring hair follicles.…”

“…38 Jackson-Boeters 2009: Periostin expression coincides with 〈-SMA expression within the granulation tissue of excisional wounds of mice. 10 Liu 2010: Inhibition of periostin expression via RNA interference suppressed proliferation of a human osteosarcoma cell line (U2OS). 39 Liu 2010: Inhibition of periostin gene expression via RNA interference suppressed migration and invasion of U2OS cells in transwell assays.…”

“…We first described the expression pattern of periostin in excisional wound healing in 2009 10 and in incisional healing in 2010. 11 In the last year, three papers have now been published describing potential roles for periostin in dermal wound repair from experiments performed using different derivations of periostin knockout mice (Postn…”