The Effect Of Lysine Acetyltransferase KAT2A On Lupus Nephritis

Objective:The effect of c GAS-STING pathway and acetyltransferase on type I interferon secretion in patients with lupus nephritis was observed to investigate its role in the inflammatory response to lupus nephritis.Methods:The study in this paper is divided into two parts.The first part explores the correlation between acetyltransferases and c GAS-STING pathway in lupus nephritis.Variation analysis,correlation analysis and KEGG pathway enrichment analysis were firstly performed on sequenced renal tissue gene samples from patients with lupus nephritis using raw letter analysis.Clinical samples were then collected for validation,and 8healthy volunteers and 18 patients with lupus nephritis were included in the control and disease groups,respectively,according to the criteria.The disease group was further divided into active(SLEDAI ≥ 15 points)and inactive groups according to the SLE Disease Activity Index(SLEDAI)score.Immunohistochemistry was used to detect intrarenal c GAS expression.Western-blot,q RT-PCR and immunofluorescence were used to detect the expression and intracellular localization of c GAS,STING and KAT2 A m RNA and protein in peripheral blood individual nuclei of each group,and to analyze the correlation between SLEDAI and c GAS and STING m RNA expression.The second part explored the effect of KAT2 A on c GAS-STING pathway and inflammatory response in lupus nephritis.Peripheral blood samples were collected from healthy volunteers and LN patients to extract single nucleated cells and divided into 4 groups:(1)HC group(3)HC-treated group(KAT2A inhibitor 1.2mol/L)(2)LN group(4)LN-treated group(KAT2A inhibitor 1.2 mol/L),and ELISA was used to detect type I interferon secretion in each group.The expression of c GAS and STING m RNA in each group after 24 h of incubation was detected by q RT-PCR.Results:1.After data processing and performing difference and correlation an alyses on the GSE112943 dataset,bioinformatics analysis showed that bot h c GAS RNA and STING RNA expression was increased in kidney tissue s of LN patients compared to healthy individuals,with statistically signifi cant differences in c GAS RNA expression.Correlation analysis of the lysi ne acetyltransferase family with c GAS-STING pathway proteins showed a positive correlation between KAT2 A and both c GAS and STING,which was subsequently verified in clinical samples.immunohistochemistry sh owed increased c GAS expression in kidney tissues of patients with IV+V lupus nephritis,and the expression was localized at the renal tubules.wes tern-blot and q RT-PCR results showed that the expression levels of c GAS m RNA and KAT2 A m RNA and protein in peripheral blood individual nu clei were significantly higher in the LN group compared to the healthy gr oup,and SLEDAI was positively correlated with KAT2 A m RNA levels w ith statistically significant differences(p<0.05),and the p-value of STING expression level was 0.1415,with no statistically significant differences between the two groups.Immunofluorescence analysis of PBMC from L N patients showed that c GAS and KAT2 A were more frequently expresse d in LN patients and both c GAS and KAT2 A were expressed in the cytopl asm.2.In the LN-treated group,c GAS and STING m RNA expression lev els in individual nucleated cells decreased after 24 h of KAT2 A inhibitor t reatment,and the differences were statistically significant(p<0.01).Δc G AS m RNA was elevated in the LN group compared to the healthy group,and ΔSTING m RNA expression was not statistically different between th e two groups.Type I interferon secretion was increased in the LN control group compared to the healthy control group.type I interferon secretion was significantly reduced in the LN-treated group compared to the LN co ntrol group(Figure 2-2a),and the difference was statistically significant(p<0.05).Compared to healthy individuals,LN patients showed more sig nificant changes in type I interferon secretion after inhibition of KAT2 A f unction,with statistically significant differences(p<0.05)Conclusion:(1)Increased expression levels of c GAS-STING pathway markers in lupus nephritis correlate with disease activity(2)Bioinformatic analysis revealed a logical correlation between KAT2 A and c GAS pathway,and increased expression of KAT2 A in PBMCs of LN patients(3)KAT2A may be involved in the inflammatory response of lupus nephritis by regulating the c GAS-STING-IFN pathway.