Lipopolysaccharide impairs gap junction function and reduces rat kidney NRK‐52E cell proliferation

Abstract

Endotoxin lipopolysaccharide (LPS)‐induced shock is life‐threatening which is often associated with acute renal failure. Gap junctions (GJ) play critical roles in maintaining kidney functions by facilitating intercellular communication and tubular purinergic signaling. However, it is unknown whether or not LPS may cause acute kidney injury by impairing renal GJ functions. Renal tubular epithelial cells are one of the main parenchymal cells that are susceptible to injurious stimuli. We, therefore, employed normal rat renal tubular epithelial cell line (NRK‐52E) to investigate the impact of LPS on cell proliferation and GJ function. NRK‐52E cells were seeded at high and low density to promote or impede GJ formation, respectively, and to establish distinctive levels of intercellular communication We found that LPS dose‐dependently reduced cell proliferation rate and colony‐formation rate of high and low density NRK‐52E cells when LPS concentration was above 100 ng/mL, accompanied with reduced connexin43 protein expression and reduced fluorescent dye transmission between adjacent cells (all p<0.05 vs. control without LPS stimulation). The GJ inhibitor oleamide attenuated LPS‐induced reduction in colony‐formation rate of high density cells, but further decreased fluorescent transmission (all P<0.05 vs. LPS). In contrast, GJ agonist retinoic acid increased fluorescent dye transmission. It is concluded that impairment in GJ function may represent a mechanism whereby LPS induces kidney cell injury.Supported by NSFC grant (No. 81170449) and Guangdong Natural Science Foundation grant (S2011020002780).