Institute of Computing Science, Poznan University of Technology, 60-965 Poznan, Poland.
Department of Medical Chemistry and Laboratory Medicine, Poznan University of Medical Sciences, 60-806 Poznan, Poland.
Int J Mol Sci. 2022 Jan 21;23(3):1189. doi: 10.3390/ijms23031189.
A deficiency of vitamin A (VAD) and iron is the most common nutritional problem affecting people worldwide. Given the scale of the problem, the interactions between vitamin A and iron levels are widely studied. However, the exact mechanism of the impact of vitamin A on the regulation of iron metabolism remains unclear. An extremely significant issue becomes a better understanding of the nature of the studied biological phenomenon, which is possible by using a systems approach through developing and analyzing a mathematical model based on a Petri net. To study the considered system, the t-cluster analysis, the significance analysis, and the analysis of the average number of transition firings were performed. The used analyses have allowed distinguishing the most important mechanisms (both subprocesses and elementary processes) positively and negatively regulating an expression of hepcidin and allowed to distinguish elementary processes with a higher frequency of occurrence compared to others. The analysis also allowed to resolve doubts about the discrepancy in literature reports, where VAD leads to positive regulation of hepcidin expression or to negative regulation of hepcidin expression. The more detailed analyses have shown that VAD more frequently positively stimulates hepcidin expression and this mechanism is more significant than the mechanism inhibiting hepcidin expression indirectly by VAD.
维生素 A(VAD)和铁缺乏是影响全世界人口的最常见营养问题。鉴于问题的规模,维生素 A 和铁水平之间的相互作用得到了广泛研究。然而,维生素 A 对铁代谢调节的影响的确切机制仍不清楚。一个极其重要的问题是通过使用系统方法通过开发和分析基于 Petri 网的数学模型来更好地理解所研究的生物现象的本质。为了研究所考虑的系统,进行了 t-聚类分析、显著性分析和平均转换发射次数分析。所使用的分析允许区分积极和消极调节铁调素表达的最重要机制(子过程和基本过程),并允许区分与其他过程相比发生频率更高的基本过程。该分析还解决了关于文献报告中不一致的疑虑,即 VAD 导致铁调素表达的正调节或铁调素表达的负调节。更详细的分析表明,VAD 更频繁地正向刺激铁调素表达,并且该机制比 VAD 间接抑制铁调素表达的机制更为重要。