Transforming growth factor-β1 in plaque morphea

Abstract

IntroductionMorphea (localized scleroderma) is a rare cutaneous disease characterized by skin fibrosis of unknown pathogenesis. Transforming growth factor-β (TGF-β) is a potent profibrotic factor. The role of TGF-β in morphea remains unclear.AimThe goal of this study was to estimate the expression level of TGF-β1 in skin and peripheral blood mononuclear cells as well as the plasma levels of TGF-β1 in plaque morphea (MEP).Material and methodsThe study involved 20 MEP patients. Three control groups were involved: 1 – plasma: 36 healthy volunteers; 2 – PBMC: 47 healthy volunteers; 3 – skin biopsies: 13 samples collected during mastectomy (breast cancer was not skin involved). The analysis of TGF-β1 plasma levels was performed with the use an adequate ELISA kit, while real-time polymerase chain reaction was employed for the expression of TGF-β1 in peripheral blood mononuclear cells (PBMC) and skin.ResultsIn our study we have not detected differences in TGF-β 1 expression in PBMC, skin, nor in plasma levels of TGF-β1 between MEP patients and healthy controls, regardless of disease activity and its duration.ConclusionsThe results of our study contradict the claim of the substantial role of TGF-β1 in the most common morphea subtype – MEP.

Differential expression of secreted factors SOSTDC 1 and ADAMTS 8 cause profibrotic changes in linear morphoea fibroblasts

“…The finding herein of unaltered levels of TGF‐β1 secretion between normal and affected fibroblasts agrees with studies investigating TGF‐β1 in skin and blood of various forms of scleroderma . Although no difference in TGF‐β1 secretion existed between normal and affected fibroblasts, there was instead a distinct response to TGF‐β1 in LM fibroblasts.…”

Evaluation of serum concentrations of the selected cytokines in patients with localized scleroderma

“…These results are in contrast to a study of Restrepo et al, who did not observe significant differences in both TGF-β1 and TGF-β2 expression in the affected skin of patients with linear scleroderma compared to healthy individuals [36]. In addition, the recent study of Dańczak-Pazdrowska et al also did not detect differences in either plasma levels of TGF-β1 or TGF-β1 expression in peripheral blood mononuclear cells and skin between patients with plaque morphea and healthy controls, regardless of disease activity and its duration [37]. Moreover, according to Uziel et al, children with LS had significantly elevated serum levels of TGF-β1 compared to controls [38].…”

CD34 stromal expression is inversely proportional to smooth muscle actin expression and extent of morphea

“…TGF-b1 is known to drive the differentiation of fibroblasts to SMA+ myofibroblasts both in vivo and in vitro, [42][43][44][45] and it plays an important role in wound healing and fibrotic diseases. 48 According to the previous in vitro studies, glucocorticoid inhibits the TGF-b1-induced phenotype transition, and in SMA+ myofibroblasts, glucocorticoid drives the glucocorticoid receptor into the nucleus and subsequently decreases transcription of pro-inflammatory genes. 48 According to the previous in vitro studies, glucocorticoid inhibits the TGF-b1-induced phenotype transition, and in SMA+ myofibroblasts, glucocorticoid drives the glucocorticoid receptor into the nucleus and subsequently decreases transcription of pro-inflammatory genes.…”

“…46,47 However, it is still unclear whether TGF-b1 really contributes to the pathogenesis of morphea, because the results of previous studies are inconsistent. 48 According to the previous in vitro studies, glucocorticoid inhibits the TGF-b1-induced phenotype transition, and in SMA+ myofibroblasts, glucocorticoid drives the glucocorticoid receptor into the nucleus and subsequently decreases transcription of pro-inflammatory genes. 49,50 Further in vivo studies are needed to elucidate a definite role of TGF-b1 and glucocorticoid in the transition of CD34+ DDCs to SMA+ myofibroblasts in morphea.…”