Recombinant SFRP5 protein significantly alleviated intrahepatic inflammation of nonalcoholic steatohepatitis
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RESEARCH
Open Access
Recombinant SFRP5 protein significantly alleviated intrahepatic inflammation of nonalcoholic steatohepatitis Lili Chen1†, Xiaolong Zhao1*†, Guangjun Liang2, Jiuru Sun2, Zhifeng Lin1, Renming Hu1, Peili Chen1, Zhaoyun Zhang1, Linuo Zhou1 and Yiming Li1
Abstract Background: Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipokine modulating metabolism dysfunction. This study aims to observe the effect of recombinant SFRP5 protein on nonalcoholic steatohepatitis (NASH). Methods: We set up a prokaryotic expression system and purified the recombinant SFRP5 protein. Recombinant SFRP5 protein was further identified by SDS-PAGE, western blot, high performance liquid chromatography (HPLC), protein mass spectrometry and in vitro Wnt5a-binding test. NASH mouse model was induced by methionine and choline deficient diet (MCDD) for 2 weeks. SFRP5 treatment group received intraperitoneal injection with a dosage of 10μg/kg SFRP5 twice a day for 2 weeks. Saline was used as control. Inflammation and fatty lesion score of liver tissue pathology and serum transaminase level were compared. Results: The purity of recombinant SFRP5 protein is 90% identified by HPLC. Its molecule size is 36,096.08 tested by mass spectrometry. Recombinant SFRP5 can specifically bind with Wnt5a which verifies its activity in vitro. The endotoxin level of this recombinant protein is 0.01EU/μg-0.1EU/μg and is suitable for animal experiment. SFRP5 can significantly improve liver inflammation (SFRP5 vs. control, 1.40 ± 0.70 vs. 2.00 ± 0.47, P < 0.05) as well as fatty lesion scores (SFRP5 vs. control, 1.40 ± 0.97 vs. 2.20 ± 0.63, P < 0.05), and lower ALT and AST levels. The mRNA expression of proinflammatory adipokines (IL-1β, IL-6, TNFα and MCP-1) in liver was down-regulated significantly after SFRP5 intervention. Immunohistochemistry and quantitative PCR revealed a dramatically down-regulation of F4/80 in liver after SFRP5 treatment. Conclusions: Recombinant SFRP5 protein significantly alleviated NASH induced by MCDD. Keywords: SFRP5, Nonalcoholic steatohepatitis, Non alcoholic fatty liver disease, Chronic inflammation
Background Due to the sedentary lifestyle and energy excess, the global pandemic of obesity further leads to an increasing prevalence of non alcoholic fatty liver disease (NAFLD) as high as approximately 30% [1, 2]. As an important component of metabolic syndrome, NAFLD is associated with cardiocerebral vascular events [2]. Moreover, NAFLD is one of the most common causes of chronic decompensated liver disease [2]. According to the natural course and * Correspondence: [email protected] † Equal contributors 1 Department of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, People’s Republic of China Full list of author information is available at the end of the article
pathologic features, NAFLD consists of 4 stages: simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NASH is the key pathophysiologic phase during NAFLD progress [
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