Title:Apigenin Alleviates Renal Fibroblast Activation through AMPK and ERK Signaling Pathways <i>In Vitro</i>
VOLUME: 21 ISSUE: 11
Author(s):Ningning Li, Zhan Wang, Tao Sun, Yanfei Lei, Xianghua Liu and Zhenzhen Li*
Affiliation:Department of Pathology, Henan Medical College, Zhengzhou, Department of Surgery, Henan Medical College, Zhengzhou, Department of Internal Medicine, Henan Medical College, Zhengzhou, Department of Traditional Chinese Medicine, Henan Medical College, Zhengzhou, Scientific Research and Experiment Center, Henan University of Traditional Chinese Medicine, Zhengzhou, Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou
Keywords:Apigenin, renal fibroblast, TGF-β1, AMP-activated protein kinase, phosphorylation, ERK.
Abstract:
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.