Int J Biol Sci 2022; 18(14):5503-5521. doi:10.7150/ijbs.72751 This issue

Research Paper

Jwa participates the maintenance of intestinal epithelial homeostasis via ERK/FBXW7-mediated NOTCH1/PPARγ/STAT5 axis and acts as a novel putative aging related gene

Xiong Li1,2,3, Jingwen Liu1,2,3, Yan Zhou1,2,3, Luman Wang1,2,3, Yifan Wen1,2,3, Kun Ding1,2,3, Lu Zou1,2,3, Xia Liu1,2,3, Aiping Li1,2,3, Yun Wang4, Heling Fu4, Min Huang5, Guoxian Ding5, Jianwei Zhou1,2,3,✉

1. Department of Molecular Cell Biology & Toxicology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
2. Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
3. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing 211166, China.
4. Animal Core Facility of Nanjing Medical University, Jiangsu Animal Experimental Center of Medical and Pharmaceutical Research, Nanjing 211166, China.
5. Department of Geriatrics, Division of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

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Citation:
Li X, Liu J, Zhou Y, Wang L, Wen Y, Ding K, Zou L, Liu X, Li A, Wang Y, Fu H, Huang M, Ding G, Zhou J. Jwa participates the maintenance of intestinal epithelial homeostasis via ERK/FBXW7-mediated NOTCH1/PPARγ/STAT5 axis and acts as a novel putative aging related gene. Int J Biol Sci 2022; 18(14):5503-5521. doi:10.7150/ijbs.72751. Available from https://www.ijbs.com/v18p5503.htm

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Abstract

Graphic abstract

The intestinal epithelium is a rapid self-renewal and regenerated tissue of which the structural integrity is beneficial for maintaining health. The integrity of intestinal epithelium depends on the balance of cell proliferation, differentiation, migration, and the function of intestinal stem cells, which declines due to genetic defect or aging. Jwa participates in multiple cellular processes; it also responds to oxidative stress and repairs DNA damage. However, whether Jwa plays a role in maintaining the homeostasis of intestinal renewal and regeneration is not clear. In the present study, we firstly described that the deletion of Jwa disturbed the homeostasis of intestinal epithelial renewal and regeneration. Jwa deficiency promoted NOTCH1 degradation in the ERK/FBXW7-mediated ubiquitin-proteasome pathway, thus disturbing the PPARγ/STAT5 axis. These mechanisms might partially contribute to the reduction of intestinal stem cell function and alteration of intestinal epithelial cell lineage distribution, finally suppressing the renewal and regeneration of intestinal epithelium. Moreover, our results also revealed that Jwa was a novel putative aging related gene.

Keywords: JWA, Intestinal epithelial homeostasis, Intestinal stem cell, Notch signal, Ubiquitination, Aging