Abstract
Osteopontin (OPN) is an extracellular matrix protein implicated in bone remodeling, but it presents also pro-inflammatory and pro-fibrotic properties. OPN expression also occurs upon exposure of cells to classical mediators of acute inflammation such as tumor necrosis growth factor alpha (TNF-α) and interleukin-1 beta (IL-1β), as well as fibrogenic cytokines such as transforming growth factor beta (TGF-β), although a detailed understanding of these regulatory pathways is still unknown. Plasma OPN levels in both limited and diffuse systemic sclerosis patients (ISSc and dSSc) were statistically higher compared to those of control subjects. Immunohistology demonstrated that high TGF-β levels, alpha smooth muscle actin (αSMA) levels and consequently high OPN levels were found in the affected skin of sclerodermic patients (ISSc and dSSc) compared to levels found in healthy skin. In order to better understand how OPN interferes with the fibrotic process, healthy skin fibroblasts were treated for 24 and 48 hours with bleomycin and with endothelin-1 (ET-1) plus TGF-β in order to induce the fibrogenesis. After 48 hours of stimulation, healthy treated fibroblasts showed statistically increased αSMA levels (index of differentiation into myofibroblasts) and simultaneously statistically increased OPN levels compared to healthy untreated ones. This study demonstrates that OPN levels increase simultaneously with the increasing of αSMA levels, therefore it is reasonable to hypothesize that OPN interferes in the pathogenesis of Systemic Sclerosis in the early stage of fibroblast differentiation process.