Departamento de Bioquímica, Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.
Departamento de Neumología, Hospital Universitario de Badajoz, Badajoz, Spain.
FASEB J. 2021 Sep;35(9):e21816. doi: 10.1096/fj.202100638R.
Proper physiological function of mammalian airways requires the differentiation of basal stem cells into secretory or multiciliated cells, among others. In addition, the self-renewal ability of these basal stem cells is crucial for developing a quick response to toxic agents in order to re-establish the epithelial barrier function of the airways. Although these epithelial missions are vital, little is known about those mechanism controlling airway epithelial regeneration in health and disease. p53 has been recently proposed as the guardian of homeostasis, promoting differentiation programs, and antagonizing a de-differentiation program. Here, we exploit mouse and human tracheal epithelial cell culture models to study the role of MDM2-p53 signaling in self-renewal and differentiation in the airway epithelium. We show that p53 protein regulation by MDM2 is crucial for basal stem cell differentiation and to keep proper cell proliferation. Therefore, we suggest that MDM2/p53 interaction modulation is a potential target to control regeneration of the mammalian airway epithelia without massively affecting the epithelium integrity and differentiation potential.
哺乳动物气道的正常生理功能需要基底干细胞分化为分泌细胞或纤毛细胞等。此外，这些基底干细胞的自我更新能力对于快速应对有毒物质以重建气道上皮屏障功能至关重要。尽管这些上皮任务至关重要，但对于控制健康和疾病中气道上皮再生的机制知之甚少。p53 最近被提出作为维持内稳态的守护者，促进分化程序，并拮抗去分化程序。在这里，我们利用小鼠和人气管上皮细胞培养模型来研究 MDM2-p53 信号在气道上皮细胞自我更新和分化中的作用。我们表明，MDM2 对 p53 蛋白的调节对于基底干细胞分化和维持适当的细胞增殖至关重要。因此，我们认为 MDM2/p53 相互作用的调节可能是控制哺乳动物气道上皮细胞再生的潜在靶点，而不会大规模影响上皮完整性和分化潜力。
