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

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.