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Huangkui capsule in combination with leflunomide improves immunoglobulin a nephropathy by inhibiting the TGF-ß1/Smad3 signaling pathway.
Pei, Shuwen; Li, Yan.
  • Pei, Shuwen; Harbin First Hospital. Department of Nephrology. Harbin. CN
  • Li, Yan; Harbin First Hospital. Intensive Care Unit. Harbin. CN
Clinics ; 76: e2904, 2021. tab, graf
Article in English | LILACS | ID: biblio-1350626
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.
Subject(s)


Full text: Available Index: LILACS (Americas) Main subject: Drugs, Chinese Herbal / Smad3 Protein / Transforming Growth Factor beta1 / Leflunomide / Glomerulonephritis, IGA Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Clinics Journal subject: Medicine Year: 2021 Type: Article Affiliation country: China Institution/Affiliation country: Harbin First Hospital/CN

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Full text: Available Index: LILACS (Americas) Main subject: Drugs, Chinese Herbal / Smad3 Protein / Transforming Growth Factor beta1 / Leflunomide / Glomerulonephritis, IGA Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Clinics Journal subject: Medicine Year: 2021 Type: Article Affiliation country: China Institution/Affiliation country: Harbin First Hospital/CN