Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Gastroenterology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
J Mol Histol. 2020 Apr;51(2):183-189. doi: 10.1007/s10735-020-09868-7. Epub 2020 Mar 21.
Liver fibrosis is a common pathological process of chronic hepatic injury, preceded by the chronic inflammation. The homeobox B13 (HOXB13) gene, a member of HOX family, plays diverse biological roles in embryonic development, carcinogenesis, and many inflammatory diseases. However, the expression of HOXB13 in chronic liver diseases including hepatic fibrosis remains to be defined. In present study, 55 patients with hepatic fibrosis, 15 patients of hepatocellular carcinoma, and 17 healthy controls were enrolled in this study. Pathological specimens were collected through liver biopsy or surgical resection. The degree of hepatic inflammation (G0-G4) and fibrosis (S0-S4) of hepatic fibrosis was scored based on the modified histology activity index. Intrahepatic HOXB13 expression was analyzed using immunohistochemistry analysis. Compared with healthy subjects, both patients with hepatic fibrosis and patients with hepatocellular carcinoma exhibited significant accumulations of HOXB13+ cells in the liver (p < 0.05). Additionally, the number of HOXB13+ cell was significantly elevated along with the increment of hepatic inflammatory activities, but not fibrosis stages, among these liver fibrosis samples (p < 0.01). Furthermore, the quantity of HOXB13+ cells were also positively correlated with hepatic enzymes, alanine transaminase (r = 0.299, p = 0.041) and aspartate aminotransferase (r = 0.317, p = 0.013) in our cohort of hepatic fibrosis. In conclusion, our study identified a strong hepatic expression of HOXB13 among patients with hepatic fibrosis, which strongly associated with the degree of hepatic inflammatory activity for patients with hepatic fibrosis, suggesting an important role of HOXB13 during the pathogenesis of liver fibrogenesis.
肝纤维化是慢性肝损伤的常见病理过程,之前是慢性炎症。同源盒 B13(HOXB13)基因是 HOX 家族的成员,在胚胎发育、致癌作用和许多炎症性疾病中发挥着多样化的生物学作用。然而,HOXB13 在包括肝纤维化在内的慢性肝病中的表达仍有待确定。在本研究中,纳入了 55 例肝纤维化患者、15 例肝细胞癌患者和 17 名健康对照者。通过肝活检或手术切除收集病理标本。根据改良组织学活动指数对肝纤维化的肝炎症(G0-G4)和纤维化(S0-S4)程度进行评分。采用免疫组织化学分析检测肝内 HOXB13 的表达。与健康受试者相比,肝纤维化患者和肝细胞癌患者的肝组织中均有显著的 HOXB13+细胞堆积(p<0.05)。此外,在这些肝纤维化样本中,随着肝炎症活性的增加,HOXB13+细胞的数量显著增加,但与纤维化阶段无关(p<0.01)。此外,HOXB13+细胞的数量与肝酶丙氨酸氨基转移酶(r=0.299,p=0.041)和天冬氨酸氨基转移酶(r=0.317,p=0.013)在肝纤维化患者中呈正相关。总之,本研究在肝纤维化患者中发现了 HOXB13 的强烈肝表达,其与肝纤维化患者的肝炎症活性程度密切相关,提示 HOXB13 在肝纤维化发病机制中具有重要作用。