Function and potential mechanism of microvesicles (MVs) containing microRNA34a in renal interstitial fibrosis were investigated. A rat model of renal interstitial fibrosis was established by unilateral ureteral ligation (UUO). Rat proximal tubular epithelial cell line (NRK-52E) was used to explore the effect of MVs containing microRNA-34a on tubular epithelial cells during fibrosis, which were secreted by tubulointerstitial fibroblasts. Regardless of the UUO renal interstitial fibrosis model, or the TGF-β1-treated renal tubular epithelial cells, microRNA-34a was increased in the MVs secreted by tubulointerstitial fibroblasts. miR-34a could be transmitted through the damaged tubule basement membrane to proximal tubular epithelial cells, where it induced apoptosis of renal tubular epithelial cells by inhibiting the expression of Bcl-2, further aggravating renal interstitial fibrosis. MicroRNA-34a secreted by damaged renal interstitial fibroblasts can promote renal tubular epithelial cell apoptosis and participate in renal interstitial fibrosis by inhibiting Bcl-2.
The present meta-analysis aimed to systematically review the efficacy and safety of belimumab (BLM) therapy for patients with active and autoantibody-positive systemic lupus erythematosus (SLE) treated with standard of care (SOC). To evaluate the efficacy and safety of BLM plus SOC treatment in patients with active SLE, eligible studies were retrieved from the Web of Science, The Cochrane Library, PubMed and Embase online databases up to July, 2021. Review Manager (version 5.3) and STATA 16.0 software were used to analyze the extracted data from the included studies. A total of seven randomized controlled trials (RCTs) and 19 case series, with 4,235 and 2,597 patients with SLE, respectively were analyzed. In the RCTs, there were more SLE responder index (SRI-4) responders in the BLM group compared with the control group [52.8 vs. 41.6%; relative risk (RR), 1.27; 95% confidence interval (95% CI), 1.18-1.37); P<0.00001]. In addition, compared with the placebo group, more patients in the BLM group achieved a ≥4-point reduction in the Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index score (RR, 1.26; 95% CI, 1.15-1.38; P<0.00001). Furthermore, treatment with BLM was found to significantly decrease the risk of severe disease exacerbations (flares) compared with the control group (RR, 0.72; 95% CI, 0.63-0.81; P<0.00001). Additionally, the corticosteroid dosage was reduced by ≥25 or 50% to ≤7.5 mg/day during weeks 40-52 in more patients in the BLM group compared with the control group (RR, 1.44; 95% CI, 1.17-1.76; P= 0.0005). However, no differences were observed in the RR of adverse events (AEs) and severe AEs between both groups (RR, 1.00; 95% CI, 0.97-1.02; P= 0.84; and RR, 0.80; 95% CI, 0.62-1.03; P= 0.08, respectively). In the case series studies, the total remission rate was 60.5% (95% CI, 52.1-68.3%; P= 0.015). In addition, treatment with BLM significantly decreased the use of corticosteroids (mean deviation, -8.73; 95% CI, -11.07 to -6.39; P<0.00001). Overall, the results of the present meta-analysis demonstrated that BLM therapy provided significant clinical efficacy and it was well-tolerated by patients with active SLE. More importantly, treatment with BLM may reduce the use of glucocorticoids.
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