Chilosi M, Doglioni C
Department of Pathology, University of Verona, Italy.
Sarcoidosis Vasc Diffuse Lung Dis. 2001 Mar;18(1):23-6.
The p63 gene has high homology with p53, but more complex physiologic functions, including the regulation of the maintenance of basal cells in stratified epithelia. These cells in fact express high levels of the deltaN-terminal truncated isoforms of the p63 gene that can act as dominant-negative inhibiting the activity of p53. Basal cells in human bronchi and bronchioli seem to use the same strategy, since they constitutively express high levels of p63, at variance with alveolar pneumocytes. Over-expression of these isoforms in airway basal cells can inhibit important functions of the p53-pathway, including cell cycle arrest and apoptosis. This finding underlines the key role of p63 in epithelial renewal in human lung, with important implications in the understanding of the mechanisms of tissue remodelling occurring in diffuse lung diseases.
p63基因与p53具有高度同源性，但具有更复杂的生理功能，包括调节复层上皮中基底细胞的维持。事实上，这些细胞高水平表达p63基因的N端截短异构体，其可作为显性负性因子抑制p53的活性。人类支气管和细支气管中的基底细胞似乎采用相同的策略，因为它们组成性地高水平表达p63，这与肺泡上皮细胞不同。这些异构体在气道基底细胞中的过表达可抑制p53通路的重要功能，包括细胞周期停滞和细胞凋亡。这一发现强调了p63在人类肺上皮更新中的关键作用，对理解弥漫性肺疾病中发生的组织重塑机制具有重要意义。
