Hayes Kyle, Wright Dale
Mallinckrodt Pharmaceuticals, Bridgewater, New Jersey, USA.
Physiol Rep. 2025 Apr;13(7):e70321. doi: 10.14814/phy2.70321.
Acthar® Gel (repository corticotropin injection) is an alternative treatment for patients with focal segmental glomerulosclerosis (FSGS) who cannot tolerate or do not adequately respond to glucocorticoids or calcineurin inhibitors. We compared the effects of Acthar versus methylprednisolone (MP) on gene expression in the kidney cortex in a rat model of FSGS induced by puromycin. Female Sprague-Dawley rats (6-8 weeks old) were treated for 8 weeks with Acthar 60 IU/kg (n = 5), MP 2 mg/kg (n = 5), or control (n = 4). On Day 56, animals were sacrificed, and RNA samples of kidney cortex tissue were analyzed using microarrays. Compared with control, Acthar significantly decreased the expression of more genes related to inflammation, immune function, and fibrosis than MP. A subset of these genes exhibited significantly larger fold changes in expression after treatment with Acthar versus MP, including C1qb and C1qc (complement cascade), Ccr2 and Tcrb (immune function), and Mfap4 and Vim (fibrosis). These results suggest that Acthar acts as an immunomodulator with a distinct mechanism of action from that of MP. Their differential alteration of gene expression in the kidney cortex suggests that Acthar may be more effective than MP in reducing inflammation and fibrosis in FSGS, which could slow disease progression.
促肾上腺皮质激素凝胶（长效促肾上腺皮质激素注射液）是一种针对局灶节段性肾小球硬化症（FSGS）患者的替代治疗方法，这些患者无法耐受糖皮质激素或钙调神经磷酸酶抑制剂，或对其反应不佳。我们在嘌呤霉素诱导的FSGS大鼠模型中比较了促肾上腺皮质激素与甲泼尼龙（MP）对肾皮质基因表达的影响。将6至8周龄的雌性斯普拉-道利大鼠分为三组，分别用60IU/kg促肾上腺皮质激素（n = 5）、2mg/kg MP（n = 5）或作为对照（n = 4）进行为期8周的治疗。在第56天，处死动物，并使用微阵列分析肾皮质组织的RNA样本。与对照组相比，促肾上腺皮质激素比MP显著降低了更多与炎症、免疫功能和纤维化相关基因的表达。在用促肾上腺皮质激素治疗后，这些基因中的一部分在表达上的变化倍数明显大于MP治疗后的变化倍数，包括C1qb和C1qc（补体级联反应）、Ccr2和Tcrb（免疫功能）以及Mfap4和Vim（纤维化）。这些结果表明，促肾上腺皮质激素作为一种免疫调节剂，其作用机制与MP不同。它们在肾皮质中基因表达的差异改变表明，促肾上腺皮质激素在减轻FSGS的炎症和纤维化方面可能比MP更有效，这可能会减缓疾病进展。
