Fall of PARP3 restrains Lgr5+ intestinal stem cells proliferation and mucosal renovation in intestinal aging.

Xiuying Peng, Huiling Liu, Jiancheng Wang, Jie Jiang, Hainan Chen, Jin Tao, Bin Wu

Mechanisms of ageing and development 2023 Apr

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The regeneration ability of intestinal epithelium is degenerated in aging. The determining factor is leucine-rich repeat-containing G-protein-coupled receptor 5-positive intestinal stem cells (Lgr5+ ISCs). Lgr5-EGFP (enhanced green fluorescence protein) knock-in in transgenic mice at three different ages (young group: 3-6 months; middle group: 12-14 months; old group: 22-24 months) were used to examined Lgr5+ ISCs at three different timepoints. The jejunum samples were collected for histology, immunofluorescence analysis, western blotting and PCR. In tissue, crypt depth, proliferating cells and Lgr5+ ISC numbers were increased in the middle group (12-14 months) and decreased in the old group (22-24 months). The number of proliferating Lgr5+ ISCs gradually decreased as the mice aged. In organoids, the budding number, projected area, and Lgr5+ ISC ratio decreased as the mice aged. The gene expression of poly (ADP-ribose) polymerase 3 (Parp3) and the protein expression of PARP3 were increased in the middle- and old-aged groups. PARP3 inhibitors slowed organoid growth in the middle group. In conclusion, PARP3 is upregulated in aging, and the inhibition of PARP3 reduces the proliferation of aging Lgr5+ ISCs. Copyright © 2023 Elsevier B.V. All rights reserved.

Citation

Xiuying Peng, Huiling Liu, Jiancheng Wang, Jie Jiang, Hainan Chen, Jin Tao, Bin Wu. Fall of PARP3 restrains Lgr5+ intestinal stem cells proliferation and mucosal renovation in intestinal aging. Mechanisms of ageing and development. 2023 Apr;211:111796