Fall of PARP3 restrains Lgr5+ intestinal stem cells proliferation and mucosal renovation in intestinal aging. (April 2023)

• Record Type: Journal Article
• Authors: Peng, Xiuying; Liu, Huiling; Wang, Jiancheng; Jiang, Jie; Chen, Hainan; Tao, Jin; Wu, Bin
• Is Part Of: Mechanisms of ageing and development. Volume 211(2023)
• Publication Date: 2023-04
• Subjects: Aging -- Intestinal stem cell -- Organoids -- PARP3 -- RNA-seq; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2023.111796
• Languages: English
• ISSNs: 0047-6374

Abstract

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. Graphical Abstract: From young to middle age, the crypt depth, Lgr5 + ISCs and proliferating cell numbers are increased, which is related to upregulation of PARP3. From middle age to old age, although the expression of PARP3 remained high, the Lgr5 + ISC and proliferation cell numbers decreased, causing the villi height to decrease. Lgr5 + stem cells and intestinal aging ga1 Highlights: The number of Lgr5 + ISCs increases in middle age and decreases in old age. The proliferating ability of Lgr5 + ISCs decreases gradually from young age to old age. The expression of PARP3 increases from middle age in Lgr5 + ISCs. Inhibition of PARP3 restrains the growth of middle-aged organoids.