TRIM29 promotes podocyte pyroptosis in diabetic nephropathy through the NF-kB/NLRP3 inflammasome pathway.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Gradual loss of podocytes is a sign of DN and pyroptosis mechanistically correlates with podocyte injury in DN; however, the mechanism(s) involved remain unknown. Here we reveal that TRIM29 is overexpressed in high glucose (HG)-treated murine podocytes cells and that TRIM29 silencing significantly inhibits podocyte damage due to HG treatment, as evidenced by lower desmin expression and greater nephrin expression. Additionally, flow cytometry analysis showed that TRIM29 silencing significantly inhibited HG treatment-induced pyroptosis, which was confirmed by immunoblotting for NLRP3, active Caspase-1, GSDMD-N, and phosphorylated NF-κB-p65. Conversely, overexpression of TRIM29 could trigger pyroptosis that was attenuated by NF-κB inhibition, indicating that TRIM29 promotes pyroptosis through the NF-κB pathway. Mechanistic studies revealed that TRIM29 interacts with IκBα to mediate its ubiquitination-dependent degradation, which in turn leads to NF-κB activation. Taken together, our data demonstrate that TRIM29 can promote podocyte pyroptosis by activating the NF-κB/NLRP3 pathway. Thus, TRIM29 represents a potentially novel therapeutic target that may also be clinically relevant in the management of DN.

FOXM1-activated SIRT4 inhibits NF-κB signaling and NLRP3 inflammasome to alleviate kidney injury and podocyte pyroptosis in diabetic nephropathy.

Forkhead box M1 (FOXM1) has been reported to play a protective role against acute kidney injury by driving tubular regeneration. This study aims to probe the function of FOXM1 in diabetic nephropathy (DN) and the molecules involved. FOXM1 was poorly expressed in DN-diseased kidney tissues. A murine model of DN was established, and podocytes cells (MPC5) were treated with high-glucose (HG) for in vitro studies. FOXM1 overexpression improved kidney function and reduced pathological changes in mice, and it increased the expression of the podocyte marker Nephrin in kidney tissues. In vitro, FOXM1 increased viability and reduced pyroptosis of the HG-treated MPC5 cells, and it elevated the expression of the podocyte marker Nephrin whereas reduced the expression of pyroptosis-related NLRP3 inflammasome and cleaved caspase 1. FOXM1 bound to the promoter of sirtuin 4 (SIRT4) to induce transcriptional activation. Downregulation of SIRT4 blocked the protective roles of FOXM1 both in vivo and in vitro. Phosphorylation of nuclear factor-kappa B (NF-κB) in HG-treated cells was suppressed by FOXM1 but restored after SIRT4 inhibition. In conclusion, this study suggested that FOXM1 transcriptionally activates SIRT4 and inhibits NF-κB signaling and the NLRP3 inflammasome to alleviate kidney injury and podocyte pyroptosis in DN.

Concentration and atmospheric transport of PM2.5-bound polycyclic aromatic hydrocarbons at Mount Tai, China.

Atmospheric PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) pose a major threat to human health. At present, studies on PAHs in the atmosphere have mostly focused on their concentration levels and source apportionment, whereas studies on the vertical transport of PAHs in the atmosphere are limited. However, the vertical transport of PAHs is important for their diffusion near the ground and their long-range transport at higher altitude. In this study, PM2.5 samples were collected simultaneously at the summit and foot of Mount Tai (MTsummit and MTfoot, respectively) from May to June 2017, and the concentrations of 18 PAHs in the samples were determined. The total concentration of PAHs at MTsummit was 2.406 ng m-3, which was well below the pollution levels of domestic cities, whereas that at MTfoot was as high as 9.068 ng m-3, which was within the range of pollution levels in domestic cities. The total carcinogenic risk for both MTsummit and MTfoot was within the potential risk range. Given the source of PAHs and the diurnal variation of the planetary boundary layer, the PAHs showed opposite diurnal trends at MTsummit and MTfoot. Vertical transport was an important source of daytime PAHs at MTsummit, and the vertical transport efficiency of PAHs decreased with an increasing ring number; this may be due to the combined effects of gas-particle partitioning and chemical reactions. Furthermore, PAHs originating in the surrounding high-emission provinces can affect the Mount Tai area via atmospheric trans-regional transport, and the BaP/BeP ratio is a useful indicator of the transport distance of PAHs.