Department of Dermatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan.
Arch Dermatol Res. 2013 May;305(4):325-31. doi: 10.1007/s00403-012-1307-4. Epub 2012 Dec 12.
Tie1 is an endothelial cell-specific tyrosine kinase receptor, which maintains vascular integrity and regulates angiogenesis via modulating angiopoietin/Tie2 signaling. Since the altered angiogenesis is closely related to the developmental process of systemic sclerosis (SSc), we herein investigated the clinical significance of serum soluble Tie1 (sTie1) levels and the expression levels of Tie1 in dermal microvascular endothelial cells (DMECs) in patients with SSc. Although serum sTie1 levels were comparable among total SSc, diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and healthy controls, SSc patients with decreased serum sTie1 levels had significantly shorter disease duration than those with serum sTie1 levels not decreased. In SSc patients with disease duration of >6 years, the prevalence of clinical symptoms associated with proliferative vasculopathy, such as digital ulcers, scleroderma renal crisis, and elevated right ventricular systolic pressure, was significantly higher in patients with decreased serum sTie1 levels than in those with serum sTie1 levels not decreased. In immunohistochemistry, Tie1 expression was reduced in DMECs of SSc patients with disease duration of <3 years compared with those of healthy controls. Collectively, in SSc patients with short disease duration, decreased serum sTie1 levels may reflect the down-regulation of Tie1 in DMECs. The decrease in serum sTie1 levels may serve as a marker of proliferative vasculopathy in SSc with disease duration of >6 years.
Tie1 是一种内皮细胞特异性酪氨酸激酶受体，通过调节血管生成素/Tie2 信号通路来维持血管完整性并调节血管生成。由于血管生成的改变与系统性硬化症 (SSc) 的发育过程密切相关，因此我们在此研究了 SSc 患者血清可溶性 Tie1（sTie1）水平和真皮微血管内皮细胞（DMECs）中 Tie1 表达水平的临床意义。虽然 SSc 患者的血清 sTie1 水平在总 SSc、弥漫性皮肤 SSc（dcSSc）、局限性皮肤 SSc（lcSSc）和健康对照组之间无差异，但血清 sTie1 水平降低的 SSc 患者的疾病持续时间明显短于血清 sTie1 水平未降低的患者。在疾病持续时间>6 年的 SSc 患者中，与增生性血管病变相关的临床症状（如手指溃疡、硬皮病肾危象和右心室收缩压升高）的患病率在血清 sTie1 水平降低的患者中明显高于血清 sTie1 水平未降低的患者。在免疫组化中，与健康对照组相比，疾病持续时间<3 年的 SSc 患者的 DMECs 中 Tie1 表达减少。总之，在疾病持续时间较短的 SSc 患者中，血清 sTie1 水平降低可能反映了 DMECs 中 Tie1 的下调。血清 sTie1 水平的降低可能是疾病持续时间>6 年的 SSc 中增生性血管病变的标志物。
