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. 2023 Apr:211:111796.
doi: 10.1016/j.mad.2023.111796. Epub 2023 Mar 2.

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

Xiuying Peng  1 , Huiling Liu  1 , Jiancheng Wang  2 , Jie Jiang  1 , Hainan Chen  3 , Jin Tao  1 , Bin Wu  4
Affiliations

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

Xiuying Peng et al. Mech Ageing Dev. 2023 Apr.

Abstract

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.

Keywords: Aging; Intestinal stem cell; Organoids; PARP3; RNA-seq.

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Conflict of interest statement

Conflict of Interest There are no conflicts of interest between the authors.

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