STING upregulation mediates ferroptosis and inflammatory response in lupus nephritis by upregulating < em > TBK1 < /em > and activating NF- κB signal pathway

J Biosci. 2024;49:9.ABSTRACTAccumulated evidence implicates lipid peroxidation as a key mechanism contributing to the pathogenesis of lupus nephritis (LN). Ferroptosis is a specialized form of cell death induced by loss or deficient activity of the glutathione peroxidase 4 (GPX4) and decreased clearance of polyunsaturated fatty acid hydroperoxides. STING production may lead to the occurrence of intracellular lipid peroxidation, ultimately triggering ferroptosis, but it has not been clarified whether STING can aggravate LN via ferroptosis. The adjacent normal kidney tissues from renal cell carcinoma and biopsied kidney tissue samples from LN patients were used for research, and the expression of STING protein in kidney tissue was detected by immunohistochemistry and RT-qPCR. MRL/lpr mice, a model of LN, were used to detect STING expression in kidney tissue. STING expression in the kidney tissue of MRL/lpr mice was knocked down by sh-STING-AAV, and then levels of 4-HNE, MDA, ROS, iron ion, blood urea nitrogen and serum creatinine, IL-6, IL-1β, and TNF-α, and the protein expression of STING, TBK1, NF-κB, GPX4, ACSL4, and SLC7A11 were subsequently examined. STING was elevated in the kidney tissue of LN patients and MRL/lpr mice. Compared with the MRL/lpr group, liproxstatin-1 or ferrostatin-1 treatment alleviated ferroptosis-related indicators 4-HNE, MDA, ROS, iron ion release, and GPX4 and SLC7A1 expression, whereas the treatment enhanced ACSL4 expression. STING interference ...
Source: Journal of Biosciences - Category: Biomedical Science Authors: Source Type: research