Wound healing and fibrosis: a contrasting role for periostin in skin and the oral mucosa

Abstract

Both skin and oral mucosa are characterized by the presence of keratinized epithelium in direct apposition to an underlying collagen-dense connective tissue. Despite significant overlap in structure and physiological function, skin and the oral mucosa exhibit significantly different healing profiles in response to injury. The oral mucosa has a propensity for rapid restoration of barrier function with minimal underlying fibrosis, but in contrast, skin is associated with slower healing and scar formation. Modulators of cell function, matricellular proteins have been shown to play significant roles in cutaneous healing, but their role in restoration of the oral mucosa is poorly defined. As will be discussed in this review, over the last 12 years our research group has been actively investigating the role of the profibrotic matricellular protein periostin in tissue homeostasis and fibrosis, as well as healing, in both skin and gingiva. In the skin, periostin is highly expressed in fibrotic scars and is upregulated during cutaneous wound repair, where it facilitates myofibroblast differentiation. In contrast, in gingival healing, periostin regulates extracellular matrix synthesis but does not appear to be associated with the transition of mesenchymal cells to a contractile phenotype. The significance of these findings will be discussed, with a focus on periostin as a potential therapeutic to augment healing of soft tissues or suppress fibrosis.

Periodontal Wound Healing and Tissue Regeneration: A Narrative Review

“…The skin and gingiva, typical body covering tissues, are considered structurally and functionally homogenous tissues showing similar healing patterns in response to injury. Both are characterized by the presence of keratinized epithelium with underlying connective tissue, which acts as a barrier to microorganisms and other contaminants [ 9 ].…”

“…Recent research has revealed the molecular differences between oral and skin wound healing. Most studies have suggested that an oral wound is in the “primed” state for wound healing compared to a skin wound ( Table 1 ) [ 9 , 15 , 16 , 17 ].…”

The Cellular Stress Response Interactome and Extracellular Matrix Cross-Talk during Fibrosis: A Stressed Extra-Matrix Affair

“…Interestingly, there are few physiological paradigms where wounds heal scarlessly or with minimal scarring, for instance the wounds in the early gestation fetus and in the oral mucosa of mammals heal without scar [6] the transition from scarless to scarred healing occurs in humans during late weeks of gestation [7]. A recent study showed that dermal fibroblasts with a scarring phenotype when transplanted into oral mucosa ended up generating more scar-like connective tissue compared with oral mucosal fibroblasts transplanted into the dermis [8]. The oral mucosal fibroblasts were shown to possess a higher baseline production capacity of several ECM-associated proteins than the skin fibroblasts, except type III collagen, which could be possibly attributed to a more favorable wound healing in oral mucosa [9].…”

Role of periostin in skin wound healing and pathologic scar formation

“…It is expressed in various normal tissues, often associated with fibroblasts, and involved in remodeling of the extracellular matrix environment. [ 1 , 2 ] In some disease states, such as myocardial infarction, cancer, liver fibrosis, and pathologic scarring of the skin, periostin is reportedly a vital regulator of the progression of the disease and significantly over-expressed. [ 3 ] This article summarizes recent advancements in studies on the role of periostin in skin wound healing and pathologic scar formation.…”

“…Previous studies have reported the positive function of periostin in promoting proliferation and differentiation of fibroblasts, keratinocytes, and mesenchymal cells in the wound, resulting in appropriate re-epithelialization and myofibroblast differentiation in the granulation tissue, thus gradually closing the wound. [ 1 , 6 , 9 ] Elliott et al [ 6 ] reported that full-thickness skin wounds were significantly larger in periostin-knockout mice than those in wild type mice at 5 and 7 days after wounding, and α-smooth muscle actin (α-SMA) was significantly down-regulated in wounds of periostin-deficient-mice. Moreover, Ontsuka et al [ 7 ] reported that the intervals for wound closure were significantly extended in periostin-knockout mice than those in wild type mice, suggesting that periostin could affect wound re-epithelialization.…”