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Title: [Roles of transforming growth factor - β1 and heat shock protein 47 in progression of Schistosoma japonicum-induced hepatic fibrosis].
Author: Yong-Hua Z, Chen X, Ying-Ying Y, Cong-Jin M, Pan-Pan D, Xue S, Yong-Liang X, Xiao-Lin F, Jun-Qi Y, Li-Juan S.
Journal: Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi; 2019 Sep 25; 31(4):382-387. PubMed ID: 31612672.
Abstract:
OBJECTIVE: To investigate the dynamic expression of transforming growth factor-β1 (TGF-β1) and heat shock protein 47 (HSP47) and explore their roles in the progression of hepatic fibrosis induced by Schistosoma japonicum infection. METHODS: Fifty female mice of the ICR strain were randomly divided into the infection group and the normal control group, of 25 mice in each group. Each mouse in the infection group was infected with 20 ± 1 cercariae of S. japonicum via the abdominal skin, while uninfected animals served as normal control. Five mice were sacrificed 4, 6, 8, 10 and 12 weeks post-infection and liver tissues were sampled. Serum HSP47 and TGF-β1 was determined using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of liver specimens were observed with hematoxylin & eosin (HE) staining. In addition, the synthesis of alpha 1 chain of type I collagen (COL1A1) was measured using Masson staining, and the mRNA expression of TGF-β1, HSP47 and COL1A1 was determined using real-time fluorescent quantitative PCR (qPCR) assay. RESULTS: During the period of S. japonicum-induced hepatic fibrosis, the serum HSP47 and TGF-β1 levels and the mRNA expression of TGF - β1, HSP47 and COL1A1 gradually increased with the progression of hepatic fibrosis. The serum levels of HSP47 and TGF-β1 were (179.26 ± 29.87) pg/mL and (22.37 ± 5.21) ng/mL 6 weeks post-infection, respectively, which were significantly greater than those [(150.29 ± 34.91) pg/mL and (18.54 ± 7.78) ng/mL, respectively] in the normal control group (both P values < 0.05). In addition, the mRNA expression of HSP47, COL1A1 and TGF-β1 was (0.86 ± 0.04), (1.17 ± 0.06) and (0.64 ± 0.13) in mouse liver specimens, which was significantly higher than that (0.23 ± 0.03, 0.20 ± 0.02 and 0.38 ± 0.02) in the normal control group (all P values < 0.01). CONCLUSIONS: The expression of TGF-β1 and HSP47 during the period of S. japonicum-induced hepatic fibrosis is consistent with the progression of the hepatic fibrosis, and exhibits the same tendency with type I collagen expression. HSP47 is a novel promising diagnosis marker and therapeutic target for S. japonicum-induced hepatic fibrosis. [摘要] 目的观察在日本血吸虫诱导的小鼠肝纤维化进程中转化生长因子-β1 (Transforming growth factor-β1, TGF-β1) 和热休克蛋白47 (Heat shock protein 47, HSP47) 的动态表达, 探讨其在日本血吸虫病肝纤维化发生发展中的作用。方法 将50只雌性ICR小鼠随机分成感染组和正常对照组, 每组25只。感染组每只小鼠经腹部皮肤感染日本血吸虫尾蚴 (20 ± 1) 条, 对照组以不含尾蚴的去氯水处理。分别于感染后4、6、8、10周和12周等5个时间点, 各取5只小鼠肝组织。应用酶联免疫吸附试验检测各小鼠血清中HSP47和TGF-β1含量, 肝组织HE染色观察病理学改变, Masson染色观察胶原增生情况, 应用实时荧光定量PCR检测肝组织TGF-β1、HSP47、I型胶原 (α1) 链COL1A1 基因mRNA 表达水平。结果在日本血吸虫诱导小鼠肝纤维化过程中, 小鼠血清HSP47和TGF-β1浓度和肝组织中TGF-β1 mRNA、HSP47 mRNA、COL1A1 mRNA表达水平均随纤维化进展而渐次升高。小鼠感染后6周, 小鼠血清HSP47和TGF-β1含量分别为 (179.26±29.87) pg/mL和 (22.37 ± 5.21) ng/mL, 显著高于同期正常对照组小鼠的 (150.29 ± 34.91) pg/mL和 (18.54 ± 7.78) ng/mL (P 均< 0.05)。肝组织中HSP47 mRNA、COL1A1 mRNA、TGF-β1 mRNA 表达水平分别为 (0.86 ± 0.04)、(1.17 ± 0.06) 和 (0.64 ± 0.13), 均高于同期正常对照组小鼠的 (0.23 ± 0.03)、(0.20 ± 0.02) 和 (0.38 ± 0.02) (P 均< 0.01)。结论 TGF-β1和HSP47 在日本血吸虫诱导的小鼠肝纤维进程中的表达与肝纤维化进程一致, 且随I型胶原的增多呈升高趋势; HSP47有望成为日本血吸虫病肝纤维化的新诊断标志物和治疗靶点。.

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