TACI Ig Fusion Protein Inhibits TLR4/MyD88/NF-κB Pathway Alleviates Renal Injury in IgA Nephropathy Rats
DOI:
https://doi.org/10.52547/a63wam88Keywords:
TACI Fusion, Protein, IgA Nephropathy, Rats, Inflammatory DamageAbstract
Introduction. To evaluate the impact of TACI fusion protein (TACI-Ig) on IgA nephropathy (IgAN) in rats, and to explore its mechanism and relationship with TLR4/MyD88/NF-κB pathway. Method. Sprague Dawley(SD)rats were divided into six groups: control, model, TACI-Ig low dose (TACI-Ig-L), medium dose (TACI-Ig-M), high dose (TACI-Ig-H), and prednisone acetate (PAT) group. The control group and model group received physiological saline injections, while the TACI-Ig groups were administered doses of 7.18, 14.36, and 28.72 mg/kg of TACI-Ig, respectively. PAT group was pretreated with prednisone acetate. After 8 weeks, kidney weight/body weight ratios, 24-hour urine protein (24 h UP), serum creatinine (SCr), and blood urea nitrogen (BUN) levels were measured. Additionally, concentrations of B cell activating factor (BAFF), APRIL, and Gd-IgA1 were evaluated by using ELISA. Pathological changes in kidney tissues were scored, and TLR4, MyD88, NF-κB expression levels were detected through western blot (WB) and RT-qPCR.
Results. Renal function assessments showed that the IgAN model group exhibited increased in 24 h UP, SCr, BUN, and elevated serum levels of BAFF, APRIL, Gd-IgA1, alongside higher TLR4/MyD88/NF-κB protein expression. TACI-Ig treatment significantly reduced proteinuria, SCr, BUN, levels of BAFF, APRIL, and Gd-IgA1 in IgAN rats. Pathologically, TACI-Ig ameliorated glomerular mesangial deposition and fibrosis. It also inhibited TLR4/MyD88/NF-κB protein expression, demonstrating anti-inflammatory and immune regulatory effects.
Conclusions. TACI-Ig mitigates renal injury in IgAN rats by reducing inflammatory infiltration and IgA deposition and suppressing the pathway of TLR4/MyD88/NF-κB, offering data for developing effective treatments for IgAN.
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