Abstract
OBJECTIVES:To investigate the efficacy and potential molecular mechanism of Huangkui capsule in combination with leflunomide (HKL) for the treatment of immunoglobulin A nephropathy (IgAN)METHODS:IgAN rat models were constructed by treating rats with bovine serum albumin, lipopolysaccharide, and tetrachloromethane. Th22 cells were isolated from the blood samples of patients with IgAN using a CD4+ T cell isolation kit. The expression levels of the components of the TGF-β1/Smad3 signaling pathway, namely, TGF-β1, Smad2, Smad3, Smad4, and Smad7, were detected using quantitative reverse transcription polymerase chain reaction. Cell proliferation was determined using the MTT assay, cell viability was determined using the WST 1 method, and the chemotaxis of Th22 cells was observed using the wound healing assay. Changes in the histology of the kidney tissues were analyzed using hematoxylin and eosin staining.RESULTS:Compared with IgAN rats, the rats subjected to HKL treatment showed good improvement in kidney injuries, and the combined drug treatment performed much better than the single-drug treatment. In addition, following HKL treatment, the viability, proliferation, and chemotaxis of Th22 cells dramatically decreased (*p<0.05, **p<0.01, and ***p<0.001). In addition, CCL20, CCL22, and CCL27 levels decreased and the expression of the key components of the TGF-β1/Smad3 signaling pathway was downregulated in IgAN rats and Th22 cells (*p<0.05, ***p<0.001).CONCLUSIONS:By targeting the TGF-β1/Smad3 signaling pathway, HKL treatment can improve kidney injury in IgAN rats as well as the excessive proliferation and metastasis of Th22 cells.
Highlights
Primary immunoglobulin A nephropathy (IgAN) is one of the most common glomerular diseases in children and teenagers and is mainly characterized by proteinuria, filtration membrane injury, and glomerulonephritis [1,2]
The results showed that IgAN rats constructed by the CCl4 method showed no obvious abnormalities in ALT, AST, ALB, and prothrombin time (PT) indicators (Figure S1A–D)
These results suggest that the use of Huangkui capsule in combination with leflunomide (HKL) in the treatment of IgAN rats had a positive effect on the improvement of renal pathology
Summary
Primary immunoglobulin A nephropathy (IgAN) is one of the most common glomerular diseases in children and teenagers and is mainly characterized by proteinuria, filtration membrane injury, and glomerulonephritis [1,2]. In China, the development of IgAN is the major cause of end-stage kidney diseases [3,4,5]. Delayed or inappropriate treatment of patients with IgAN in the early stage resulted in permanent disability in approximately 30% of these patients [4,6]. There is insufficient evidence regarding the pathogenesis of IgAN, which prevents the development of efficient strategies for the treatment of IgAN.
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