Department of Basic Medical Science 1, Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai 71800, Malaysia.
Department of Physiology, School of Medicine, University of Galway, H91 TK33 Galway, Ireland.
Int J Mol Sci. 2023 Jun 28;24(13):10774. doi: 10.3390/ijms241310774.
The hepatic matrisome is involved in the remodeling phase of liver regeneration. As the gut microbiota has been implicated in liver regeneration, we investigated its role in liver regeneration focusing on gene expression of the hepatic matrisome after partial hepatectomy (PHx) in germ-free (GF) mice, and in GF mice reconstituted with normal gut microbiota (XGF). Liver mass restoration, hepatocyte proliferation, and immune response were assessed following 70% PHx. Hepatic matrisome and collagen gene expression were also analyzed. Reduced liver weight/body weight ratio, mitotic count, and hepatocyte proliferative index at 72 h post PHx in GF mice were preceded by reduced expression of cytokine receptor genes and , and gene at 3 h post PHx. In XGF mice, these indices were significantly higher than in GF mice, and similar to that of control mice, indicating normal liver regeneration. Differentially expressed genes (DEGs) of the matrisome were lower in GF compared to XGF mice at both 3 h and 72 h post PHx. GF mice also demonstrated lower collagen expression, with significantly lower expression of , , and compared to WT mice at 72 h post PHx. In conclusion, enhanced liver regeneration and matrisome expression in XGF mice suggests that interaction of the gut microbiota and matrisome may play a significant role in the regulation of hepatic remodeling during the regenerative process.
肝脏基质体参与肝脏再生的重塑阶段。由于肠道微生物群与肝脏再生有关，我们研究了其在肝脏再生中的作用，重点关注无特定病原体（GF）小鼠部分肝切除（PHx）后和用正常肠道微生物群重建的 GF 小鼠（XGF）中肝脏基质体的基因表达。在进行 70% PHx 后评估了肝质量恢复、肝细胞增殖和免疫反应。GF 小鼠 PHx 后 72 小时的肝重/体重比、有丝分裂计数和肝细胞增殖指数降低，这与 PHx 后 3 小时细胞因子受体基因和基因表达降低有关。在 XGF 小鼠中，这些指数明显高于 GF 小鼠，与对照小鼠相似，表明正常的肝脏再生。与 XGF 小鼠相比，GF 小鼠基质体的差异表达基因（DEGs）在 PHx 后 3 小时和 72 小时均较低。GF 小鼠的胶原蛋白表达也较低，与 PHx 后 72 小时的 WT 小鼠相比，、、和基因的表达明显较低。总之，XGF 小鼠增强的肝脏再生和基质体表达表明，肠道微生物群和基质体的相互作用可能在调节再生过程中的肝重塑中发挥重要作用。
