No abstract

No abstract

Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes. However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosis-related proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

Background: Long-term excessive drinking can cause various harms to the human body. Alcoholic fatty liver is the manifestation of early liver lesions mainly induced by alcohol. Di-(2-ethylhexyl) phthalate, as one of the environmental internal-secretion interfering-substance, is widely used in industrial processing and various consumer goods. Large quantities of epidemiological investigations and studies have shown that frequent exposure to high concentrations of DEHP may be a potential risk factor for liver function. Methods: We used DEHP to expose alcohol-induced fatty liver rats to study the effect of DEHP on alcoholic fatty liver. Results: The results found that DEHP exposure prominently accelerated hepatic steatosis, inflammation and oxidant stress, and activates signaling pathways involved in liver inflammation and oxidative stress-related proteins expression. Studies have suggested that cytochrome P450 2E1 and silent information regulator-1 are closely related to the occurrence of alcoholic fatty liver disease. Interestingly, the trend observed in the LO-2 cells assay was consistent with the in vivo conditions. Conclusions: DEHP may promote or aggravate the progression of alcoholic fatty liver disease through CYP2E1, SIRT1 and p38 mitogen-activated protein kinase (p38MAPK) / nuclear factor-kappa B signaling pathways. And this experimental study warns us that the environmental pollutants DEHP and its potential toxicity hazards to the human body are worthy of attention.