Department of Joint Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
Clin Exp Rheumatol. 2012 Jan-Feb;30(1):39-44. Epub 2012 Mar 6.
Evidence indicates that the hyperplasia and inflammation of synovial tissues are significantly related to the pathogenic process of ankylosing spondylitis (AS). Using a proteomics approach, we detected a significantly increased expression of alpha 1-anti-trypsin (ATA1) in synovial membranes of patients with AS.
We continued to investigate the expression level and location of ATA1 in synovial tissue of AS. We also investigated the genetic effect of the gene encoding ATA1 on AS. Western blot analysis was applied to determine the expression of ATA1 in synovial tissues by comparing the expression profiles of AS (n=8), rheumatoid arthritis (RA, n=9) and osteoarthritis (OA, n=9) samples. Immunohistochemistry was used to localise the expression of ATA1 in the synovial membrane. Taqman method was used to genotype tag SNPs (rs2753934, rs2749531 and rs6575424) with 56 AS cases, 260 RA cases and 160 healthy controls.
We detected an increased expression of ATA1 in synovial membranes of AS as compared with samples from RA and OA. We immuno-localised the significant expression of ATA1 in AS tissues. No significant association was found between the ATA1 polymorphism and AS or RA. Haplotype analysis did not reveal a haplotype to be associated with AS or RA.
It has been reported that ATA1 is related with inflammation and new bone formation, two important features of AS. The current findings suggest that ATA1 contributes to the pathogenesis of AS by up-regulating the gene expression in the synovial tissues.
有证据表明,滑膜组织的增生和炎症与强直性脊柱炎(AS)的发病过程密切相关。我们采用蛋白质组学方法,在 AS 患者的滑膜组织中发现α 1-抗胰蛋白酶(ATA1)的表达显著增加。
我们继续研究 ATA1 在 AS 滑膜组织中的表达水平和位置。我们还研究了编码 ATA1 的基因对 AS 的遗传影响。通过比较 AS(n=8)、类风湿关节炎(RA,n=9)和骨关节炎(OA,n=9)样本的表达谱,应用 Western blot 分析来确定 ATA1 在滑膜组织中的表达。免疫组化用于定位 ATA1 在滑膜膜中的表达。Taqman 法用于对 56 例 AS 病例、260 例 RA 病例和 160 例健康对照进行标签 SNP(rs2753934、rs2749531 和 rs6575424)的基因分型。
与 RA 和 OA 样本相比,我们在 AS 滑膜组织中检测到 ATA1 的表达增加。我们免疫定位了 AS 组织中 ATA1 的显著表达。ATA1 多态性与 AS 或 RA 之间没有显著关联。单倍型分析未发现与 AS 或 RA 相关的单倍型。
已有报道称 ATA1 与炎症和新骨形成有关,这是 AS 的两个重要特征。目前的研究结果表明,ATA1 通过上调滑膜组织中的基因表达,促进 AS 的发病机制。