Orthopedic Center of Chinese PLA, Urumqi General Hospital of Lanzhou Military Region, Urumqi, Xinjiang, China.
Physiol Res. 2013;62(6):691-9. doi: 10.33549/physiolres.932441. Epub 2013 Jul 17.
Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles due to multiple etiologies. The main pathologic process is characterized by proliferation of fibroblasts and excessive accumulation of collagen in the extracellular matrix of the muscle. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid and has been reported to be associated with various fibrotic diseases. However, the role of S1P in GMC remains unknown. Here in this article, High-performance liquid chromatography and immunohistochemistry were applied to evaluate S1P localization and expression in clinical samples from patients with GMC, Quantitative real time PCR, Western blot, and enzyme-linked immunosorbent assay were used to explore the link between transforming growth factor-beta1 (TGF-beta1), plasminogen activator inhibitor-1 (PAI-1) and S1P. The results showed that S1P was enhanced in contraction band (CB) tissues. Studies using the cell proliferation and transformation assay indicated that exogenous S1P stimulated CB fibroblast proliferation in a time-dependent manner and in higher concentration also in a dose-dependent manner. Furthermore, we demonstrated that S1P not only promoted collagen type I production, but also up-regulated mRNA and protein expression of transforming growth factor-beta1 and plasminogen activator inhibitor-1. These findings suggest that S1P may regulate increased synthesis of collagen and other fibrogenic factors, and significantly contributes to the process of gluteal muscle scarring in patients with GMC.
臀肌挛缩症(GMC)是一种由多种病因引起的臀肌慢性纤维性疾病。主要的病理过程特征是成纤维细胞增殖和细胞外基质中胶原过度积累。鞘氨醇-1-磷酸(S1P)是一种生物活性鞘脂,据报道与多种纤维性疾病有关。然而,S1P 在 GMC 中的作用尚不清楚。在本文中,我们应用高效液相色谱法和免疫组织化学法评估了 S1P 在 GMC 患者临床标本中的定位和表达,应用定量实时 PCR、Western blot 和酶联免疫吸附试验探讨转化生长因子-β1(TGF-β1)、纤溶酶原激活物抑制剂-1(PAI-1)与 S1P 之间的关系。结果表明,S1P 在收缩带(CB)组织中增强。细胞增殖和转化试验研究表明,外源性 S1P 以时间依赖性和浓度依赖性方式刺激 CB 成纤维细胞增殖。此外,我们证明 S1P 不仅促进了 I 型胶原的产生,而且还上调了转化生长因子-β1 和纤溶酶原激活物抑制剂-1 的 mRNA 和蛋白表达。这些发现表明,S1P 可能调节胶原和其他纤维生成因子的合成增加,并显著促进 GMC 患者臀肌瘢痕形成过程。