Objective: Renal fibrosis is a common pathway leading to the progression of chronic kidney disease. Activated fibroblasts contribute remarkably to the development of renal fibrosis. Although apigenin has been demonstrated to play a protective role from fibrotic diseases, its pharmacological effect on renal fibroblast activation remains largely unknown.

Materials and Methods: Here, we examined the functional role of apigenin in the activation of renal fibroblasts response to transforming growth factor (TGF)-β1 and its potential mechanisms. Cultured renal fibroblasts (NRK-49F) were exposed to apigenin (1, 5, 10 and 20 μM), followed by the stimulation of TGF-β1 (2 ng/mL) for 24 h. The markers of fibroblast activation were determined. In order to confirm the anti-fibrosis effect of apigenin, the expression of fibrosis-associated genes in renal fibroblasts was assessed. As a consequence, apigenin alleviated fibroblast proliferation and fibroblastmyofibroblast differentiation induced by TGF-β1.

Results: Notably, apigenin significantly inhibited the fibrosis-associated genes expression in renal fibroblasts. Moreover, apigenin treatment significantly increased the phosphorylation of AMP-activated protein kinase (AMPK). Apigenin treatment also obviously reduced TGF-β1 induced phosphorylation of ERK1/2 but not Smad2/3, p38 and JNK MAPK in renal fibroblasts.

Conclusion: In a summary, these results indicate that apigenin inhibits renal fibroblast proliferation, differentiation and function by AMPK activation and reduced ERK1/2 phosphorylation, suggesting it could be an attractive therapeutic potential for the treatment of renal fibrosis.

目的：肾纤维化是导致慢性肾脏疾病进展的常见途径。活化的成纤维细胞显着促进肾纤维化的发展。尽管芹菜素已被证明对纤维化疾病起保护作用，但其对肾成纤维细胞活化的药理作用仍然未知。

材料和方法：在这里，我们检查了芹菜素在激活肾成纤维细胞对转化生长因子（TGF）-β1的反应中的功能作用及其潜在机制。将培养的肾成纤维细胞（NRK-49F）暴露于芹菜素（1、5、10和20μM），然后刺激TGF-β1（2 ng / mL）24小时。确定了成纤维细胞活化的标志物。为了证实芹菜素的抗纤维化作用，评估了肾成纤维细胞中纤维化相关基因的表达。结果，芹菜素减轻了由TGF-β1诱导的成纤维细胞增殖和成纤维细胞肌成纤维细胞分化。

结果：芹菜素显着抑制肾成纤维细胞中纤维化相关基因的表达。此外，芹菜素处理显着增加了AMP激活的蛋白激酶（AMPK）的磷酸化。芹菜素处理还明显降低了TGF-β1诱导的肾成纤维细胞ERK1 / 2的磷酸化，但不降低Smad2 / 3，p38和JNK MAPK的磷酸化。

结论：综上所述，这些结果表明芹菜素通过AMPK激活抑制肾成纤维细胞的增殖，分化和功能，并减少ERK1 / 2磷酸化，表明其可能具有治疗肾纤维化的诱人治疗潜力。