The Diabetes-Linked Transcription Factor PAX4: From Gene to Functional Consequences.
The Diabetes-Linked Transcription Factor PAX4: From Gene to Functional Consequences.
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DOI：
10.3390/genes8030101
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发表时间：
2017-03-09
期刊：
影响因子：
3.5
通讯作者：
Gauthier BR
中科院分区：
文献类型：
--
作者：
Lorenzo PI;Juárez-Vicente F;Cobo-Vuilleumier N;García-Domínguez M;Gauthier BR
配对框4（PAX4）是在胚胎发育期间产生胰岛素产生β细胞的关键因子。在成年胰岛中，PAX4表达被隔离到倾向于增殖并且对应激诱导的细胞凋亡更具抗性的β细胞亚群。PAX4突变与糖尿病发展的相关性已经证明了这种转录因子对胰岛功能的重要性，而与其病因无关。这种因子在成年胰岛中的过表达刺激β细胞增殖并增加其对凋亡的抵抗力。此外，在自身免疫性糖尿病的实验模型中，已经提出了该因子的新的免疫调节功能。总之，这些数据将PAX4确定为糖尿病治疗的新型再生疗法的重要靶标，旨在保存剩余的β细胞，同时刺激其增殖，以补充疾病进展期间丢失的β细胞群。然而，这种疗法的充分发展需要了解控制PAX4表达的分子机制以及可以解释PAX4作用的下游效应物。
Paired box 4 (PAX4) is a key factor in the generation of insulin producing β-cells during embryonic development. In adult islets, PAX4 expression is sequestered to a subset of β-cells that are prone to proliferation and more resistant to stress-induced apoptosis. The importance of this transcription factor for adequate pancreatic islets functionality has been manifested by the association of mutations in PAX4 with the development of diabetes, independently of its etiology. Overexpression of this factor in adult islets stimulates β-cell proliferation and increases their resistance to apoptosis. Additionally, in an experimental model of autoimmune diabetes, a novel immunomodulatory function for this factor has been suggested. Altogether these data pinpoint at PAX4 as an important target for novel regenerative therapies for diabetes treatment, aiming at the preservation of the remaining β-cells in parallel to the stimulation of their proliferation to replenish the β-cell mass lost during the progression of the disease. However, the adequate development of such therapies requires the knowledge of the molecular mechanisms controlling the expression of PAX4 as well as the downstream effectors that could account for PAX4 action.