Abdellatif Hussein, Al Jabri Ruqaiya, Albalushi Halima, Al Mushaiqri Mohamed
Department of Human and Clinical Anatomy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman.
Anat Cell Biol. 2025 Jun 30;58(2):247-263. doi: 10.5115/acb.24.231. Epub 2025 Jan 15.
Liver regeneration is intricate, involves many cells, and necessitates extended research. This study aimed to investigate the response of liver oval cells (bipotent liver progenitors) to the epigenetic modifier trichostatin A (TSA), an HDAC1 inhibitor, and to develop a scoring system for assessing the response of these cells. Three groups of equally divided rats (n=24) were selected: control (A, dimethyl sulfoxide treated); oval cell induction (B, acetylaminofluorene [2-AAF] to block hepatocyes/carbon tetrachloride [CCL4] to induce oval cell response); and epigenetic modulation (C, TSA post 2-AAF/CCL4 injury). The oval cell response was quantified using immunoreactivity to the OV-6 antibody, and the ductular response was measured by calculating the bile duct (BD) to portal vein (PV) ratio and the percentage of individual oval cells in liver sections. The expression level of HDAC1 was also analyzed. The administration of TSA significantly enhanced oval cell proliferation and the ductular response (6.13±0.28). The control group exhibited limited immunoreactivity to OV-6, while group B showed significant induction of ductular response with distinct morphology (4.13±0.28). The expression levels of HDAC1 were elevated in both the oval cell induction group and the epigenetic modulation group compared to the control group. This study developed a precise method for quantifying liver oval cells and analyzing their response to TSA. TSA administration enhanced oval cell proliferation, suggesting its significance in regulating hepatic progenitor cell dynamics. The findings support the use of epigenetic modifiers in liver regeneration and propose a scoring system for assessing the response of liver oval cells.
肝脏再生过程错综复杂，涉及多种细胞，需要进行深入研究。本研究旨在探究肝脏卵圆细胞（双能肝脏祖细胞）对表观遗传修饰剂曲古抑菌素A（TSA，一种HDAC1抑制剂）的反应，并建立一个评分系统来评估这些细胞的反应。选取三组数量均等的大鼠（n = 24）：对照组（A组，用二甲基亚砜处理）；卵圆细胞诱导组（B组，用2-乙酰氨基芴[2-AAF]阻断肝细胞/用四氯化碳[CCL4]诱导卵圆细胞反应）；表观遗传调控组（C组，在2-AAF/CCL4损伤后给予TSA）。使用对OV-6抗体的免疫反应性来量化卵圆细胞反应，通过计算肝切片中胆管（BD）与门静脉（PV）的比例以及单个卵圆细胞的百分比来测量小胆管反应。还分析了HDAC1的表达水平。给予TSA显著增强了卵圆细胞增殖和小胆管反应（6.13±0.28）。对照组对OV-6的免疫反应性有限，而B组显示出明显的小胆管反应诱导，形态明显（4.13±0.28）。与对照组相比，卵圆细胞诱导组和表观遗传调控组中HDAC1的表达水平均升高。本研究开发了一种精确的方法来量化肝脏卵圆细胞并分析它们对TSA的反应。给予TSA可增强卵圆细胞增殖，表明其在调节肝祖细胞动态方面的重要性。这些发现支持在肝脏再生中使用表观遗传修饰剂，并提出了一个评估肝脏卵圆细胞反应的评分系统。
