Disulfide-bond A oxidoreductase-like protein (DsbA-L) is an adiponectin- interacting protein that is highly expressed in adipose tissue. The adipo-renal axis involves adipocyte release of signaling molecules that are recruited to kidney and regulate kidney function. We have found that the DsbA-L modulated the progression of diabetic nephropathy, but the precise mechanism of this modulation is unknown. Here, the transgenic mice overexpressing DsbA-L protein in fat (fDsbA-L) were used to verify that the renoprotective role of DsbA-L whether by adipo-renal axis. Mice were divided into four groups: a normal (Control) group, STZ induced diabetic mice , fDsbA-L mice and diabetic fDsbA-L mice (n=6). Diabetes was induced in mice by STZ 100mg/kg and continued HFD feeding for 12 weeks. Compared with the control group, the weight, blood glucose,and urine protein levels and the pathological changes in the kidney tissue of diabetic mice were increased significantly, accompanied by increased NLRP3,caspase-1, IL-1, IL-18, FN, and Collagen1 mRNA and protein expression, which were reduced in diabetic fDsbA-L mice. Interestingly, the level of adiponectin in serum and kidney expression in diabetic mice was reduced significantly compared to that in the control group. However this change was reversed in diabetic fDsbA-L mice. These data suggest that the overexpression of DsbA-L in the adipocytes of mice can protect against diabetic renal injury through anti-inflammatory mediators,and may be mediated by the adipo-renal axis.

中文翻译：

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DsbA-L可防止通过肾肾轴对糖尿病肾的损害

二硫键类似的氧化还原酶蛋白（DsbA-L）是在脂肪组织中高度表达的脂联素相互作用蛋白。脂肪肾轴涉及脂肪细胞释放的信号分子，这些分子被募集到肾脏并调节肾脏功能。我们已经发现DsbA-L调节了糖尿病性肾病的进展，但是这种调节的确切机制尚不清楚。在这里，使用在脂肪中过表达DsbA-L蛋白的转基因小鼠（fDsbA-L）来验证DsbA-L的肾保护作用是否通过脂肪肾轴。将小鼠分为四组：正常（对照组），STZ诱导的糖尿病小鼠，fDsbA-L小鼠和糖尿病性fDsbA-L小鼠（n ＝ 6）。STZ 100mg / kg在小鼠中诱发糖尿病，并持续喂食HFD 12周。与对照组相比，体重，血糖，糖尿病小鼠肾脏中尿蛋白水平和病理变化显着增加，伴随而来的是NLRP3，caspase-1，IL-1，IL-18，FN和Collagen1 mRNA和蛋白表达的增加，而在糖尿病小鼠中则降低了fDsbA-L小鼠。有趣的是，与对照组相比，糖尿病小鼠血清和肾脏表达中脂联素的水平明显降低。但是，这种变化在糖尿病性fDsbA-L小鼠中被逆转。这些数据表明，DsbA-L在小鼠脂肪细胞中的过表达可以通过抗炎介质来预防糖尿病性肾损伤，并且可能由脂肪肾轴介导。在糖尿病性fDsbA-L小鼠体内，胶原蛋白mRNA和蛋白表达降低。有趣的是，与对照组相比，糖尿病小鼠血清和肾脏表达中脂联素的水平明显降低。然而，这种变化在糖尿病性fDsbA-L小鼠中被逆转。这些数据表明，DsbA-L在小鼠脂肪细胞中的过表达可以通过抗炎介质来预防糖尿病性肾损伤，并且可能由脂肪肾轴介导。在糖尿病性fDsbA-L小鼠体内，胶原蛋白mRNA和蛋白表达降低。有趣的是，与对照组相比，糖尿病小鼠血清和肾脏表达中脂联素的水平明显降低。然而，这种变化在糖尿病性fDsbA-L小鼠中被逆转。这些数据表明，DsbA-L在小鼠脂肪细胞中的过表达可以通过抗炎介质来预防糖尿病性肾损伤，并且可能由脂肪肾轴介导。