Background Scleroderma impairs patients’ quality of life and frequently threatens patients’ lives. There is still no established treatment for the fibrosis in scleroderma.Elucidation of the underlying cause of this disease has been much awaited. Recently, the matricellular molecules and their associated molecules in skin were suggested to play key roles in scleroderma, and the studies on them are still on-going.
Objectives Periostin, a novel matricellular protein, is recently reported to paly a crucial role in tissue remodeling, and highly expressed in fibrotic conditions. This study was undertaken to assess the role of periostin in scleroderma.
Methods Using patients and healthy donors’ skin tissues, expression of periostin was assessed by immunohistochemistry and immunoblotting analysis. Furthermore, we investigated periostin-/- (PN-/-) mice and wild-type (WT) mice to elucidate the role of periostin in scleroderma. To induce murine cutaneous sclerosis, mice were subcutaneously injected with bleomycin, while untreated control groups were injected with phosphate buffered saline. Bleomycin-induced fibrotic changes were compared between PN-/-and WT mice, by histologic analysis, as well as measuring profibrotic cytokines and extracellular matrix proteins (ECM) expression in vivo and in vitro. To determine the downstream signal transduction pathway for the effect of exogenous periostin, signal-transduction inhibitors were used in vitro.
Results Elevated expression of periostin was observed in lesional skin of patients with scleroderma, compared with healthy donors. Regarding the animal experiments, although WT mice showed marked cutaneous sclerosis with increased expression of periostin and increased number of myofibroblasts by bleomycin treatment, PN-/- mice showed resistant to these changes. In vitro, PN-/- mice dermal fibroblasts showed reduced transcripts expression of transforming growth factor beta 1 (TGFβ1)-induced alpha smooth muscle actin (αSMA) and procollagen type I alpha 1 (Col1α1). Furthermore, recombinant mouse periostin directly induced Col1α1 expression in vitro, and this effect was inhibited by PI3K/Akt kinase inhibitor LY294002.
Conclusions Periostin plays an essential role in the pathogenesis of scleroderma.
Disclosure of Interest None Declared
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