Modified Huangqi Chifeng decoction alleviates IgA nephropathy inflammation and renal fibrosis via miR-146a/TLR4/NF-κB
Yue Shi1,2, Jing Liu3, Sijia Ma4
1Department of Nephrology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Background:
Immunoglobulin A nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide and a leading cause of end-stage renal disease, posing a significant threat to human health. Modified Huangqi Chifeng decoction (MHCD) has shown efficacy in ameliorating IgAN; however, its underlying regulatory mechanisms remain incompletely understood.
Objective:
To evaluate the anti-inflammatory and anti-fibrotic effects of MHCD on IgAN and elucidate its molecular mechanisms through in vivo and in vitro experiments.
Methods:
An IgAN rat model was established. The therapeutic effects of MHCD were assessed by measuring 24-hour urinary protein, Gd-IgA1, serum biochemistry, renal pathological damage, IgA deposition, inflammatory mediators, and fibrosis levels after 8 weeks of MHCD administration. ELISA was used to quantify inflammatory mediators; Western blot and immunohistochemistry were employed to analyze protein expression; PCR was performed to determine miR-146a levels. Subsequently, lipopolysaccharide-stimulated mesangial cells were used in vitro. Mesangial cell proliferation and the expression of TLR4/NF-κB signaling pathway components and downstream inflammatory factors was examined to verify the anti-inflammatory and anti-fibrotic mechanism of MHCD by overexpressing or silencing miR-146a.
Results:
MHCD reduced urinary protein and serum Gd-IgA1 in IgAN rats, and alleviated renal IgA deposition, pathological injury, inflammation and fibrosis. Furthermore, MHCD inhibited renal expression of TLR4, MyD88, NF-κB p65 and NF-κB p-p65, and increased the level of miR-146a. Mechanistically, in vitro experiments demonstrated that MHCD exerted anti-inflammatory and anti-fibrotic effects by upregulating miR-146a and inhibiting the TLR4/NF-κB signaling pathway.
Conclusion:
MHCD alleviates IgA nephropathy inflammation and renal fibrosis partially through upregulating miR-146a and subsequently suppressing the TLR4/NF-κB signaling pathway.
