Zhang Jian, Li Junhong, Ma Junwei, Wang Hongxin, Yi Yin
Emergency Department, Beijing You'an Hospital, Capital Medical University, Beijing 100069, P.R. China.
Exp Ther Med. 2018 Apr;15(4):3189-3196. doi: 10.3892/etm.2018.5840. Epub 2018 Feb 6.
Hepatitis B cirrhosis is caused by liver cell necrosis, residual liver cell nodular regeneration, connective tissue hyperplasia and fiber formation, which frequently leads to adrenal insufficiency. Previous reports have demonstrated that human fibroblast growth factor (hFGF)-21 is a multifunctional protein that exhibits potential therapeutic value for metabolic diseases. The present study investigated the diagnostic value of hFGF-21 and analyzed the potential molecular mechanism in the progression of hepatitis B cirrhosis combined with adrenal insufficiency. Characteristics of cellular immunity and humoral immunity were analyzed in patients with hepatitis B cirrhosis combined with adrenal insufficiency (PhbA). Results demonstrated that expression levels of hFGF-21 were downregulated in plasma and liver cells isolated from clinical specimens. Plasma concentration levels of hFGF-21 were upregulated in prognostic PhbA. assays indicated that hFGF-21 treatment decreased the continuous deposition of extracellular matrix and reactive oxygen species in liver cells isolated from clinical specimens. Results also demonstrated that hFGF-21 treatment downregulated inflammatory cytokines. It was observed that hFGF-21 treatment downregulated nuclear factor (NF)-κB and Kruppel-like factor 6. Notably, transforming growth factor (TGF)-β, platelet-derived growth factor and epidermal growth factor levels were improved by hFGF-21 treatment. In conclusion, these results indicated that hFGF-21 inhibits inflammation by regulation of the NF-κB-mediated TGF-β signaling pathway, which may serve as a predictor and prognostic factor in PhbA.
乙型肝炎肝硬化是由肝细胞坏死、残留肝细胞结节状再生、结缔组织增生和纤维形成引起的,常导致肾上腺功能不全。先前的报道表明,人成纤维细胞生长因子(hFGF)-21是一种多功能蛋白,对代谢性疾病具有潜在的治疗价值。本研究探讨了hFGF-21的诊断价值,并分析了其在乙型肝炎肝硬化合并肾上腺功能不全进展中的潜在分子机制。对乙型肝炎肝硬化合并肾上腺功能不全患者(PhbA)的细胞免疫和体液免疫特征进行了分析。结果表明,从临床标本中分离的血浆和肝细胞中hFGF-21的表达水平下调。预后良好的PhbA患者血浆中hFGF-21浓度水平上调。检测表明,hFGF-21处理可减少从临床标本中分离的肝细胞中细胞外基质和活性氧的持续沉积。结果还表明,hFGF-21处理可下调炎性细胞因子。观察到hFGF-21处理可下调核因子(NF)-κB和Kruppel样因子6。值得注意的是,hFGF-21处理可改善转化生长因子(TGF)-β、血小板衍生生长因子和表皮生长因子水平。总之,这些结果表明,hFGF-21通过调节NF-κB介导的TGF-β信号通路抑制炎症,这可能是PhbA的一个预测指标和预后因素。