Background: The causal relationship between physical activity (PA) and systemic lupus erythematosus (SLE) remains uncertain. We aimed to assess the causal effect of PA on SLE by two-sample Mendelian randomization (MR) study.Methods: Summary statistics of SLE were obtained from a genome-wide association study (GWAS) meta-analysis of European descent, including 4,036 cases and 6,959 controls. Genetic instruments for PA, including MVPA, VPA, SSOE, and average acceleration, were identified from a large-scale GWAS meta-analysis among 377,234 individuals of European ancestry from United Kingdom biobank and Atherosclerosis Risk in Communities (ARIC) study, and another GWAS with 91,105 European participants was employed for sedentary behavior. The two-sample MR study was conducted to estimate causal relationship between PA and SLE, with the inverse-variance weighted (IVW) method, simple- and weighted-median method. Moreover, MR-Egger regression, MR-PRESSO and leave-one-out analysis were performed to evaluate the potential pleiotropy effect.Results: In the end, we totally selected 37 SNPs (15 SNPs for MVPA, 5 SNPs for VPA, 9 SNPs for SSOE, 5 SNPs for average acceleration and 3 SNPs for sedentary behavior). According to the IVW results, as the primary method, we found that genetically predicted PA was not causally associated with risk of SLE (MVPA: OR 0.44, 95% CI 0.09–2.10, p = 0.305; VPA: OR 0.20, 95% CI 0.00–18.97, p = 0.490; SSOE: OR 0.96, 95% CI 0.03–29.24, p = 0.983; average acceleration: OR 0.91, 95% CI 0.79–1.05, p = 0.190; sedentary behavior: OR 1.54, 95% CI 0.35–6.81, p = 0.572). MR-Egger, MR-PRESSO, and leave-one-out analysis did not indicate horizontal pleiotropy.Conclusions: Our MR study suggested that genetically predicted PA was not causally associated with SLE among the European populations.

Background: Previous observational studies have suggested that the causal role of systemic lupus erythematosus (SLE) in the risk of cardiovascular diseases (CVDs) remained inconsistent. In this study, we aimed to investigate the causal relationship between SLE and CVDs by two-sample Mendelian randomization (MR) analysis.Methods: Genetic instruments for SLE were obtained from a public genome-wide association study (GWAS) with 4,036 patients with SLE and 6,959 controls. Summary statistical data for CVDs, including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), ischemic stroke (IS), and its subtypes, were identified from other available GWAS meta-analyses. The inverse-variance weighted (IVW) method was used as the primary method to estimate the causal effect. The simple- and weighted-median method, MR-Egger method, and MR pleiotropy residual sum and outlier (MR-PRESSO) were provided as a supplement to the IVW method. Besides, we performed sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis, to evaluate the robustness of the results.Results: A total of 15 single-nucleotide polymorphisms (SNPs) were identified after excluding linkage disequilibrium (LD) and potential confounding factors. According to the IVW results, our MR study indicated that genetically predicted SLE was not causally connected with the risk of CVDs [CAD: odds ratio (OR) = 1.005, 95% confidence interval (CI) = 0.986–1.024, p-value = 0.619; MI: OR = 1.002, 95% CI = 0.982–1.023, p-value = 0.854; AF: OR = 0.998, 95% CI = 0.982–1.014, p-value = 0.795; IS: OR = 1.006, 95% CI = 0.984–1.028, p-value = 0.621; cardioembolic stroke (CES): OR = 0.992, 95% CI = 0.949–1.036, p-value = 0.707; small vessel stroke (SVS): OR = 1.014, 95% CI = 0.964–1.067, p-value = 0.589; large artery stroke (LAS): OR = 1.030, 95% CI = 0.968–1.096, p-value = 0.352]. Analogical findings could be observed in supplementary MR methods. Sensitivity analyses suggested that the causal estimates were robust.Conclusion: Our two-sample MR analysis provided no evidence that genetically determined SLE was causally associated with the risk of CVDs.

Jieduquyuziyin prescription (JP) has been used to treat lupus nephritis (LN) and its effectiveness in the treatment of LN has been clinically proven, but the underlying mechanisms have yet to be completely understood. This aim of this study was to clarify the efficacy of JP on the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells and the molecular mechanisms of JP in MRL/lpr mice. In vivo, we observed the therapeutic actions of JP in MRL/lpr mice as well as its antifibrosis effect and potential mechanism. In vitro, we evaluated the role of JP in EMT and its possible mechanism through the EMT of human renal proximal tubular epithelial cells (HK-2) induced by transforming growth factor-beta 1 (TGF-β1) and M2c macrophages. HK-2 cells were treated with JP-treated serum, and MRL/lpr mice were treated by JP for 8 weeks. The results showed that JP alleviated disease activity, improved renal function, decreased proteinuria, and improved renal injury and fibrosis in MRL/lpr mice. Furthermore, JP suppressed the activation of the TGF-β1/Smad2/3 signaling pathway, upregulated the E-cadherin levels, and downregulated the Vimentin and mesenchymal α-smooth muscle actin (α-SMA) levels in the kidney of MRL/lpr mice. JP was further found to prevent the TGF-β1 and M2c macrophages-induced EMT of HK-2 cells. Collectively, JP could alleviate the disease activity of MRL/lpr mice, improve renal function, and attenuate renal fibrosis, and its underlying mechanisms may be related to the inhibition of EMT and TGF-β1/Smad2/3 signaling pathway.