Periostin induces fibroblast proliferation and myofibroblast persistence in hypertrophic scarring

Abstract

Hypertrophic scarring is characterized by the excessive development and persistence of myofibroblasts. These cells contract the surrounding extracellular matrix resulting in the increased tissue density characteristic of scar tissue. Periostin is a matricellular protein that is abnormally abundant in fibrotic dermis, however, its roles in hypertrophic scarring are largely unknown. In this report, we assessed the ability of matrix-associated periostin to promote the proliferation and myofibroblast differentiation of dermal fibroblasts isolated from the dermis of hypertrophic scars or healthy skin. Supplementation of a thin type-I collagen cell culture substrate with recombinant periostin induced a significant increase in the proliferation of hypertrophic scar fibroblasts but not normal dermal fibroblasts. Periostin induced significant increases in supermature focal adhesion formation, α smooth muscle actin levels and collagen contraction in fibroblasts cultured from hypertrophic scars under conditions of increased matrix tension in three-dimensional type-I collagen lattices. Inhibition of Rho-associated protein kinase activity significantly attenuated the effects of matrix-associated periostin on hypertrophic scar fibroblasts and myofibroblasts. Depletion of endogenous periostin expression in hypertrophic scar myofibroblasts resulted in a sustained decrease in α smooth muscle actin levels under conditions of reducing matrix tension, while matrix-associated periostin levels caused the cells to retain high levels of a smooth muscle actin under these conditions. These findings indicate that periostin promotes Rho-associated protein kinase-dependent proliferation and myofibroblast persistence of hypertrophic scar fibroblasts and implicate periostin as a potential therapeutic target to enhance the resolution of scars.

MicroRNA-185 regulates transforming growth factor-β1 and collagen-1 in hypertrophic scar fibroblasts

“…These results suggested that overexpressed miR-185 can inhibit HSFBs growth and that the underlying mechanism was mediated, at least partly, through the suppression of TGF-β1 and Col-1 expression. HS occurs as a result of a pathological wound-healing process, characterized by excess collagen deposition and hyperproliferation of fibroblasts (2,6,8). …”

“…These cells contract the surrounding extracellular matrix resulting in the increased tissue density characteristic of scar tissue, which not only affects the appearance and functions of skin, however can additionally result in psychological trauma for the patient (2). The treatment of pathological scars is difficult due to a lack of effective therapeutic options and frequently involves scar revision surgery, which can induce renewed scar formation (3,4).…”

Periostin as a multifunctional modulator of the wound healing response

“…The role of Postn in skin pathologies (Arima, et al, 2015, Crawford, et al, 2015, Mineshige, et al, 2015, Shiraishi, et al, 2012, Song and Qin, 2008, Supp, et al, 2012, Yamaguchi, et al, 2013, Zhang, et al, 2015, Zhou, et al, 2010) and wound healing (Elliott, et al, 2012a, Elliott, et al, 2012b, Jackson-Boeters, et al, 2009, Nishiyama, et al, 2011, Ontsuka, et al, 2012, Walker, et al, 2015, Zhou, et al, 2010) has been the subject of intense research, which has pointed to very specific roles for Postn.…”

“…Further evidence for the importance of Postn in skin comes from analysis of its expression patterns in scarring (Crawford, et al, 2015, Li, et al, 2013, Song and Qin, 2008, Zhang, et al, 2014, Zhou, et al, 2010) and in direct contrast, non-healing skin lesions (Elliott, et al, 2015). Postn is overexpressed in both hypertrophic and keloid scarring (Crawford, et al, 2015, Zhou, et al, 2010).…”

Fibroblast—Extracellular Matrix Interactions in Tissue Fibrosis

“…Periostin is consistently induced in activated myofibroblasts and critically regulates their matrix-synthetic function [96]. Periostin potently stimulates fibroblast proliferation and myofibroblast persistence [97]; whether its stimulatory actions involve intracellular or matricellular effects remains unknown.…”