Biochemical and Biophysical Research Communications, Vol.508, No.1, 92-96, 2019
Each liver X receptor (LXR) type has a different purpose in different situations
LXRs, which are nuclear receptors, have 2 isoforms-LXR alpha and LXR beta. Generally, LXR alpha, is expressed in the liver, kidney, and a limited number of other organs, whereas LXR beta is thought to be expressed ubiquitously. Nevertheless, no clear consensus has been reached on the role of each in kidney lipid metabolism. Many researchers have reported that lipids accumulate in renal tubular epithelial cells during nephrosis. The nephrosis model we used showed the presence of urinary protein 4 days after the induction of illness. Additionally, the model maintained high levels of urinary protein from day 7-14. Lipid accumulation was clearly verified at day 4 and extreme accumulation was observed at day 7. We observed increased expression of LXR alpha from an early stage of nephrosis. To explore the role of increased LXR alpha in diseased kidney in vitro, NRK52E, normal kidney tubular epithelial cells, were forced to overexpress LXR alpha. These cells showed significantly lower lipid accumulation than mock cells did. In contrast, LXR beta knockdown lead to increased lipid accumulation in mock cells, and constancy in overexpressing cells. In normal kidneys, LXR beta is expressed stably to control mainly the intracellular lipids. However, with increasing intracellular lipid accumulation, expression of LXR alpha and its downstream gene, ABCA1, was upregulated, followed by lipid excretion in an LXRa-dependent manner. This phenomenon strongly suggests the importance of LXR alpha in lipid metabolism in the diseased kidney. (C) 2018 Elsevier Inc. All rights reserved.