Department of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Beijing Huaxin Hospital, The First Affiliated Hospital of Tsinghua Uinversity, Beijing, China.
Gene. 2020 Mar 1;729:144233. doi: 10.1016/j.gene.2019.144233. Epub 2019 Nov 21.
Collagen β (1-O) galactosyltransferase 1 (GLT25D1) has been reported to transfer galactose to hydroxylysine residues via β (1-O) linkages in collagen. However, the role of Glt25d1 in liver fibrogenesis is still unknow. Recently, we generated a Glt25d1 knockout mouse to elucidate the role of Glt25d1 in vivo. However, we found that complete deletion of the Glt25d1 gene resulted in embryonic lethality at E11.5. Histopathological analysis revealed that dysplasia in Glt25d1 labyrinth with defects of the vascular network. Immunohistochemical showed that the decrease in proliferation of Glt25d1 liver and the developing central nervous system (CNS). The role of Glt25d1 in liver fibrogenesis was explored by Glt25d1 mice. Glt25d1 mice and wild-type (WT) mice were injected intraperitoneally with the same dose of CCl. The higher level of serum alanine aminotransferase was observed in Glt25d1 mice. Reverse transcription-quantitative polymerase chainreaction demonstrated that the mRNA expression levels of the inflammatory cytokines such as, Tnf-α, Cxcl-1 and Mcp-1, showed a significantly increase in CCl-treated Glt25d1 mice. Collagen-I, collagen-III and α-SMA transcripts accumulation was markedly increased in the Glt25d1 mice. However, Masson's trichrome staining revealed a trend to decrease in the ECM proteins deposition of Glt25d1 liver. Immunohistochemistry and Western blots revealed that the protein expression of Collagen-III was reduced and a trend to a decrease in collagen-I was observed in the Glt25d1 liver compared with those of WT mice. Our results demonstrate that Glt25d1 knockout results in embryonic lethality and down-regulation of Glt25d1 may inhibit collagen secretion during liver fibrogenesis.
胶原β(1-O)半乳糖基转移酶 1(GLT25D1)已被报道通过胶原中的β(1-O)键将半乳糖转移到羟赖氨酸残基上。然而，Glt25d1 在肝纤维化中的作用仍不清楚。最近，我们生成了 Glt25d1 敲除小鼠以阐明 Glt25d1 在体内的作用。然而，我们发现 Glt25d1 基因的完全缺失导致 E11.5 时胚胎致死。组织病理学分析显示 Glt25d1 迷路发育不良伴血管网络缺陷。免疫组织化学显示 Glt25d1 肝脏和发育中的中枢神经系统(CNS)增殖减少。通过 Glt25d1 小鼠探索 Glt25d1 在肝纤维化中的作用。Glt25d1 小鼠和野生型(WT)小鼠经腹腔注射相同剂量的 CCl。Glt25d1 小鼠的血清丙氨酸氨基转移酶水平升高。逆转录定量聚合酶链反应显示，炎性细胞因子如 Tnf-α、Cxcl-1 和 Mcp-1 的 mRNA 表达水平在 CCl 处理的 Glt25d1 小鼠中显著增加。胶原-I、胶原-III 和α-SMA 转录物的积累在 Glt25d1 小鼠中明显增加。然而，Masson 三色染色显示 Glt25d1 肝脏 ECM 蛋白沉积呈减少趋势。免疫组织化学和 Western blot 显示 Glt25d1 肝脏中 Collagen-III 的蛋白表达减少，Collagen-I 的表达也呈减少趋势与 WT 小鼠相比。我们的结果表明，Glt25d1 敲除导致胚胎致死，下调 Glt25d1 可能抑制肝纤维化过程中的胶原分泌。
