The Effect Of Acitretion On The Function Of Systemic Sclerosis Fibroblasts

Systemic sclerosis (SSc) is a connective tissue disease characterized by excessive and frequently progressive accumulation of collagen, which leads to the sclerosis of the skin as well as other internal organs. Retinoic acids were recently reported to produce significant clinical improvement in sclerotic skin manifestation of SSc. However, the therapeutical mechanism is still unknown. This study focused on the effects of acitretin on the collagen synthesis, cell proliferation, mRNA expression of pro α 1( â…  ) collagen,TGF-β₁ production in SSc dermal fibroblasts (Fb). The molecular pharmacological mechanism of acitretin in the treatment of SSc was discussed.Chapter 1. The Effect of Acitretin on Cell Proliferation in Cultured SSc Fb. Objective: To study the biological effect of acitretin on the Fb proliferation and morphology in SSc. Methods: 1. Primary culture of Fb was established from the sclerotic skin of three patients with SSc. 2. Fb was cultivated with various concentrations of acitretin (10 (-8)¹0^-5mol/L) for 48 hours, inverted microscope was used to observe the morphological alteration of Fb. 3. MTT test was used to asses cell proliferation. Results: 1. The Fb treated with acitretin for 48 hours didn't show transformable morphology. 2. Acitretin could inhibit the proliferation of Fb in a dose-dependent manner. The highest inhibition ratio was 21.74% in the presence of 10^-5M acitretin. Conclusions: 1. The various concentrations of acitretin used in the test have no effect on the morphology of Fb. 2. The excessive deposing of extra cellular matrix can be prevented by acitretin through inhibiting Fb proliferation. Chapter 2. The Effects of Acitretin on Collagen Synthesis and mRNA Expression in SSc Fb.Objective: To study acitretin on the collagen synthesis and the mRNA expression of pro α 1(â… ) collagen in SSc Fb. Methods: 1. Fb incubated with acitretin at the level of 10 (-8)¹0^-5mol/L for 48 hours. The collagen production calculated from hydroproline in the cultured medium was detected by microplate reader. 2. Fb incubated with...