Maternal endotoxemia induces renal collagen deposition in adult offspring: Role of NADPH oxidase/TGF-β1/MMP-2 signaling pathway.,Archives of Biochemistry and Biophysics

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Maternal endotoxemia induces renal collagen deposition in adult offspring: Role of NADPH oxidase/TGF-β1/MMP-2 signaling pathway.
Archives of Biochemistry and Biophysics ( IF 3.8 ) Pub Date : 2020-02-17 , DOI: 10.1016/j.abb.2020.108306
Juliane S Farias ₁ , Kelly M Santos ₁ , Natália K S Lima ₁ , Edjair V Cabral ₁ , Regina S Aires ₁ , Alana C Veras ₁ , Ana D Paixão ₁ , Leucio D Vieira ₁

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Maternal endotoxemia has been shown to increase renal collagen deposition in the offspring. Renal fibrosis is a hallmark of progressive chronic kidney disease. It was investigated whether maternal reactive oxygen species (ROS) leads to renal fibrosis or exacerbates unilateral ureteral obstruction (UUO)-induced renal fibrosis in the offspring of dams treated with lipopolysaccharide (LPS). Furthermore, it was studied the role of matrix metalloproteinases (MMPs) in these changes. Adults Wistar rats were obtained from dams submitted to LPS administration through the third part of gestation. To evaluate the role of maternal ROS, part of the dams received α-tocopherol simultaneously with LPS. Part of the offspring in each group was submitted to UUO at adulthood when sub-groups were treated with NADPH oxidase inhibitor, apocynin. Maternal LPS administration increased proteinuria, systolic arterial pressure and renal collagen deposition in adult offspring. LPS offspring rats also presented higher MMP-2 activity in parallel to a decreased renal cortical TIMP-2 content. These changes were correlated to increased amounts of TGF-β1 and NOX2. Maternal α-tocopherol treatment prevented collagen deposition and reduced arterial pressure in adult offspring. α-Tocopherol also inhibited maternal endotoxemia-induced changes in TGF-β1/NOX2/MMP-2 signaling. UUO led to increased collagen deposition in the contralateral kidneys of LPS offspring, which was correlated to increased NADPH oxidase activity and prevented by NADPH oxidase inhibition. In summary, maternal endotoxemia led to alterations in the TGF-β1/NOX2/MMP-2 signaling pathway in renal tissue concomitant with collagen deposition, therefore contributing to hypertension in adult offspring.

中文翻译：

母体内毒素血症诱导成年后代的肾胶原沉积：NADPH氧化酶/TGF-β1/ MMP-2信号通路的作用。

孕妇内毒素血症已显示会增加后代中肾胶原的沉积。肾纤维化是进行性慢性肾脏疾病的标志。研究了用脂多糖（LPS）处理的母亲的后代中母体活性氧（ROS）是导致肾纤维化还是加剧单侧输尿管阻塞（UUO）诱导的肾纤维化。此外，还研究了基质金属蛋白酶（MMP）在这些变化中的作用。成年Wistar大鼠是从妊娠第三部分开始进行LPS给药的大坝中获得的。为了评估母体ROS的作用，部分水坝同时接受了α-生育酚和LPS。每组的一部分后代在成年期接受NADPH氧化酶抑制剂阿朴西宁处理后被送入UUO。产妇LPS给药会增加成年后代的蛋白尿，收缩动脉压和肾胶原沉积。LPS后代大鼠还表现出更高的MMP-2活性，同时肾皮质TIMP-2含量降低。这些变化与TGF-β1和NOX2的增加有关。孕妇α-生育酚治疗可防止成年后代胶原蛋白沉积并降低动脉压。α-生育酚还抑制母体内毒素血症诱导的TGF-β1/ NOX2 / MMP-2信号转导的变化。UUO导致LPS后代对侧肾脏中胶原蛋白沉积的增加，这与NADPH氧化酶活性的增加相关，并被NADPH氧化酶抑制所阻止。总之，母亲内毒素血症导致肾组织中TGF-β1/ NOX2 / MMP-2信号通路的改变，并伴随胶原沉积，

更新日期：2020-02-20

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