Abstract
BackgroundPM2.5 is associated closely with an increased risk of membranous nephropathy (MN), however, whether PM2.5 could induce podocytes injury, the underlying pathology for MN, has not be thoroughly studied. Triptolide, an active component in Tripterygium wilfordii Hook F, is frequently used to treat MN in China, but its effects on PM2.5-induced podocytes injury is still largely unknown. Therefore, we evaluated the effects of PM2.5 on podocytes, and explored whether triptolide could improve PM2.5-induced podocytes injury and the possible underlying mechanisms.ResultsPodocytes were incubated with PM2.5 after being pre-treated with triptolide, viability, apoptosis rate and migratory capacity of podocytes were determined by CCK-8 assay, flow cytometry and Transwell assay, respectively. Additionally, the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) in podocytes, the cytoskeleton of podocytes, the protein expressions of nephrin, podocin, Bcl-2, Bax, nuclear factor kappa-B/p65 (NF-κB/p65) and phospho-inhibitor of NF-κB (p-IκBα) were measured. Our data showed that PM2.5 treatment significantly increased the disorganization of F-actin stress fibers, the damaged structural integrity of nucleus, the deranged and dissociated cytoskeleton in podocytes, increased the podocytes apoptosis rate, the levels of MDA and LDH, markedly up-regulated the protein expression of Bax, NF-κB/p65 and p-IκBα, down-regulated the protein expression of nephrin, podocin and Bcl-2, and significantly decreased the level of SOD, the migration rate and the viability of podocytes, compared with those of the untreated podocytes. These effects of PM2.5 on podocytes, however, were reversed by triptolide administration.ConclusionThese results suggest that triptolide could prevent against PM2.5-induced podocytes injury via suppressing NF-κB signaling pathway.
Highlights
PM2.5 is associated closely with an increased risk of membranous nephropathy (MN), whether PM2.5 could induce podocytes injury, the underlying pathology for MN, has not be thoroughly studied
On the basis of these findings, we hypothesized that the inhalation of PM2.5 could accelerate the development of MN by inducing podocytes injury, and agents attenuating podocytes injury would be potential therapeutic drugs that prevent against PM2.5-induced MN
Podocytes viability following PM2.5 or triptolide treatment In order to evaluate the podocytes injury induced by PM2.5, podocytes were stimulated with different concentrations of PM2.5 at 0, 25, 50, 100, 200 or 400 mg/L for 24 h, and podocytes were stimulated with 200 mg/L PM2.5 for 0, 3, 6, 12, 24 or 48 h
Summary
PM2.5 is associated closely with an increased risk of membranous nephropathy (MN), whether PM2.5 could induce podocytes injury, the underlying pathology for MN, has not be thoroughly studied. We evaluated the effects of PM2.5 on podocytes, and explored whether triptolide could improve PM2.5-induced podocytes injury and the possible underlying mechanisms. A pivotal pathogenesis of MN is podocytes ( called as glomerular visceral epithelial cells) injury either by creating an environment favorable to deposition and accumulation of immune complexes containing exogenous antigens or by providing a source of endogenous antigens. Once formed, these antigenantibody complexes are capped and attached to the GBM. On the basis of these findings, we hypothesized that the inhalation of PM2.5 could accelerate the development of MN by inducing podocytes injury, and agents attenuating podocytes injury would be potential therapeutic drugs that prevent against PM2.5-induced MN
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