Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Kua-hause Isawa, Isawa Onsen Hospital, Fuefuki, Yamanashi, Japan.
J Clin Endocrinol Metab. 2019 Jan 1;104(1):172-180. doi: 10.1210/jc.2017-02705.
Angiopoietin-like protein 2 (ANGPTL2) is a circulating, proinflammatory protein.
To examine the role of ANGPTL2 in the pathogenesis of diabetic kidney disease (DKD), we studied the epigenetic regulation of angptl2 expression in patients with diabetes.
DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: We determined the relationship between serum ANGPTL2 levels and the progression of DKD in cross-sectional (220 patients) and cohort (145 patients, 7-year follow-up) studies. Furthermore, we investigated the direct effect of ANGPTL2 on podocyte function.
The main outcome was progression of DKD.
We found that the expression of angptl2 was decreased by the methylation of its promoter region. Multivariate logistic regression analyses revealed that the baseline level of serum ANGPTL2 was an independent risk factor for the progression of DKD during follow-up periods. In cultured podocytes, ANGPTL2 directly increased albumin permeability through the translocation of zonula occludens-1 from the membrane to the cytosol via activation of focal adhesion kinase.
ANGPTL2 might be directly involved in podocyte dysfunction and independently associated with the progression of DKD stages.
血管生成素样蛋白 2（ANGPTL2）是一种循环的促炎蛋白。
为了研究 ANGPTL2 在糖尿病肾病（DKD）发病机制中的作用，我们研究了糖尿病患者中 angptl2 表达的表观遗传调控。
设计、环境、参与者和干预措施：我们在横断面研究（220 例患者）和队列研究（145 例患者，7 年随访）中确定了血清 ANGPTL2 水平与 DKD 进展之间的关系。此外，我们还研究了 ANGPTL2 对足细胞功能的直接影响。
主要结局是 DKD 的进展。
我们发现 angptl2 的表达受其启动子区域甲基化的抑制。多变量逻辑回归分析显示，基线血清 ANGPTL2 水平是随访期间 DKD 进展的独立危险因素。在培养的足细胞中，ANGPTL2 通过激活粘着斑激酶，将封闭蛋白-1 从膜转移到细胞质，直接增加白蛋白通透性。
ANGPTL2 可能直接参与足细胞功能障碍，并与 DKD 阶段的进展独立相关。
