Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
Nephrol Dial Transplant. 2017 Oct 1;32(10):1637-1644. doi: 10.1093/ndt/gfw472.
Follistatin-like 3 (FSTL3) is a novel cytokine that regulates insulin sensitivity and counteracts activin/myostatin signalling. In the present study, regulation of FSTL3 in renal dysfunction was investigated in both human chronic kidney disease (CKD) and acute kidney dysfunction (AKD). Furthermore, mFSTL3 expression was analysed in insulin-sensitive tissues in a mouse model of CKD.
Circulating FSTL3 was quantified by enzyme-linked immunosorbent assay in 581 patients with CKD covering the whole spectrum of estimated glomerular filtration rate (eGFR) categories from G1 to G5. Furthermore, FSTL3 was measured in 61 patients before and within 30 h after elective unilateral nephrectomy, an established model of AKD. Moreover, mFSTL3 mRNA expression was investigated in an animal CKD model, that is, eNOS-/-db/db mice, and compared with littermate controls.
Median circulating FSTL3 levels significantly and continuously increased with deteriorating renal function (eGFR category G1: 6.1; G2: 8.2; G3: 12.7; G4: 18.5; G5: 32.1 µg/L; P < 0.001). In both human CKD and AKD, renal dysfunction remained the strongest independent predictor of FSTL3 serum concentrations in multivariate analyses. FSTL3 was independently associated with an adverse cardiometabolic profile. In CKD mice, hepatic mFSTL3 mRNA expression was increased more than 6-fold as compared with controls.
Circulating FSTL3 is significantly and independently associated with renal function in both patients with CKD and AKD. Hepatic mFSTL3 mRNA upregulation might contribute to increased FSTL3 levels in CKD. Our results are in agreement with the hypothesis that FSTL3 is eliminated by the kidneys and might counteract adverse activin/myostatin signalling observed in renal dysfunction.
卵泡抑素样 3（FSTL3）是一种新型细胞因子，可调节胰岛素敏感性并拮抗激活素/肌生成素信号。本研究旨在探讨 FSTL3 在人类慢性肾脏病（CKD）和急性肾损伤（AKD）中的调控作用。此外，在 CKD 小鼠模型中分析了胰岛素敏感组织中的 mFSTL3 表达。
采用酶联免疫吸附法检测 581 例 CKD 患者（涵盖 eGFR 各亚组）的循环 FSTL3 水平。此外，在 61 例患者中测量了其术前及术后 30h 内的 FSTL3 水平，该模型为 AKD 的建立模型。同时，在 eNOS-/-db/db 小鼠的 CKD 动物模型中研究了 mFSTL3 mRNA 表达，并与同窝对照进行比较。
随着肾功能恶化（eGFR 亚组 G1：6.1；G2：8.2；G3：12.7；G4：18.5；G5：32.1µg/L；P<0.001），循环 FSTL3 水平显著且连续升高。在 CKD 和 AKD 患者中，多变量分析显示肾功能不全仍然是 FSTL3 血清浓度的最强独立预测因素。FSTL3 与不良的心血管代谢特征独立相关。与对照组相比，CKD 小鼠肝组织 mFSTL3 mRNA 表达增加了 6 倍以上。
在 CKD 和 AKD 患者中，循环 FSTL3 与肾功能显著且独立相关。肝组织 mFSTL3 mRNA 的上调可能导致 CKD 中 FSTL3 水平升高。我们的结果与 FSTL3 通过肾脏清除并可能拮抗肾功能不全中观察到的不良激活素/肌生成素信号的假说一致。
