科研之友
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摘要
Systemic sclerosis (SSc) is a connective tissue disease that results in fibrosis in multiple organs. Various animal models for this disease have been developed, both genetic and induced. One of the induced models, sclerodermatous graft-versus-host disease (scl-GvHD), exhibits the main characteristics of SSc, but involves lethal gamma-irradiation of recipients. We sought to develop a modified scl-GvHD model. Spleen cells from B10.D2 donor mice were transplanted into immunodeficient Rag-2 recipients on the BALB/c genetic background. Tissue fibrosis was analyzed at 3 and 9 weeks after transplantation. In addition to serum levels of anti-Scl-70 autoantibody and cytokines, tissue inflammation, fibrosis, expression of collagen-I and -smooth muscle actin (alpha-SMA), infiltration of leukocytes, mRNA expression of transforming growth factor (TGF)-beta, collagen-I, alpha-SMA, tumor necrosis factor (TNF)-beta, and interleukin (IL)-6, the classical signal pathway of TGF-beta, Smad-3, and p-Smad-3 expression in tissue were analyzed. Skin thickening and increased collagen synthesis, as well as the manifestation of tissue fibrosis, could be detected in skin, kidney, and lung of modified scl-GvHD mouse model. Increased serum levels of anti-Scl-70 autoantibody, IL-10, and TGF-beta could be detected. Increased CD4(+) T cells and F4/80(+) macrophage infiltration were found in skin, kidney, and lung. Gene expression of collagen-I, TGF-beta, alpha-SMA, TNF-beta, and IL-6 was increased in tissue of the scl-GvHD model. Moreover, TGF-beta expression and Smad-3 phosphorylation were detected in skin, kidney, and lung of scl-GvHD mice. Our data show that spleen cells from B10.D2 donor mice transplanted into immunodeficient Rag-2 recipients could induce typical fibrosis not only of the skin and kidney but also of lung, which was missing from previous scl-GvHD models. Thus, the modified scl-GvHD model might be a promising model to explore the immunologic mechanisms of SSc and may be useful for investigation of new therapies for systemic sclerosis.
- 出版日期2017-9
- 单位复旦大学
