Melnikova A I, Krasnova T S, Rubtsov P M
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow oblast, 141701 Russia.
Mol Biol (Mosk). 2025 Mar-Apr;59(2):189-200.
PAX4 (Paired Box 4) is a transcription factor that is expressed mainly in the pancreas and plays a key role in the development of insulin-producing β cells at the embryonic stage. In mature cells, PAX4 acts as a main regulator of their adaptation under pathological conditions. The importance of PAX4 to the proper function of pancreatic islets has been demonstrated in studies of the relationship between mutations of the PAX4 gene and various forms of diabetes mellitus (DM). PAX4 overexpression in adult islets stimulates β-cell proliferation and resistance to apoptosis. Taken together, the data indicate that PAX4 provides a potential target to develop new DM treatments aimed at reprogramming different cell types into insulin-producing cells and promoting their proliferation to replenish the β-cell pool lost during disease progression. The development of such methods requires knowledge of the molecular mechanisms that control expression of PAX4 and its target genes. The review summarizes the data on the structure and expression of the human PAX4 gene. Interactions of various transcription factors during differentiation of pancreatic cells and the formation of islets of Langerhans are described along with the role of PAX4 in the processes. Associations between mutations of human PAX4 and various DM forms were considered. A final part of the review examines the prospects for reprogramming cells of other types into insulin-producing cells and discusses the effects on PAX4- regulated signaling pathways as a means to develop new approaches to DM treatment.
PAX4（配对盒4）是一种主要在胰腺中表达的转录因子，在胚胎期胰岛素分泌β细胞的发育中起关键作用。在成熟细胞中，PAX4在病理条件下作为细胞适应性的主要调节因子发挥作用。PAX4基因的突变与各种形式的糖尿病（DM）之间关系的研究已证明了PAX4对胰岛正常功能的重要性。在成年胰岛中过表达PAX4可刺激β细胞增殖并增强其抗凋亡能力。综上所述，这些数据表明，PAX4为开发新型糖尿病治疗方法提供了一个潜在靶点，该方法旨在将不同细胞类型重编程为胰岛素分泌细胞，并促进其增殖以补充疾病进展过程中丢失的β细胞库。开发此类方法需要了解控制PAX4及其靶基因表达的分子机制。本综述总结了关于人类PAX4基因结构和表达的数据。描述了胰腺细胞分化和胰岛形成过程中各种转录因子的相互作用以及PAX4在这些过程中的作用。还探讨了人类PAX4突变与各种糖尿病形式之间的关联。综述的最后一部分研究了将其他类型细胞重编程为胰岛素分泌细胞的前景，并讨论了对PAX4调节的信号通路的影响，以此作为开发新型糖尿病治疗方法的一种手段。
