Huangkui Capsule in Combination with Leflunomide Improves Immunoglobulin A Nephropathy by Inhibiting the TGF-β1/Smad3 Signaling Pathway

Authors

DOI:

https://doi.org/10.6061/clinics/2021/e2904

Keywords:

IgA Nephropathy, Huangkui Capsules, Leflunomide, Th22 Cells, TGF-β1/Smad3 Signaling Pathway

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.

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Published

2021-12-10

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Section

Original Articles

How to Cite

Pei, S., & Li, Y. (2021). Huangkui Capsule in Combination with Leflunomide Improves Immunoglobulin A Nephropathy by Inhibiting the TGF-β1/Smad3 Signaling Pathway. Clinics, 76, e2904. https://doi.org/10.6061/clinics/2021/e2904