IL-33 Accelerates Chronic Atrophic Gastritis through AMPK-ULK1 Axis Mediated Autolysosomal Degradation of GKN1

Liu, Kewei; Huang, Hongxia; Xiong, Mengyuan; Wang, Qiaojiao; Chen, Xiantao; Feng, Yinqiong; Ma, Hang; Chen, Wanqun; Li, Xuegang; Ye, Xiaoli

doi:10.7150/ijbs.93573

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Int J Biol Sci 2024; 20(6):2323-2338. doi:10.7150/ijbs.93573 This issue Cite

Research Paper

IL-33 Accelerates Chronic Atrophic Gastritis through AMPK-ULK1 Axis Mediated Autolysosomal Degradation of GKN1

Kewei Liu^1#, Hongxia Huang^2#, Mengyuan Xiong¹, Qiaojiao Wang¹, Xiantao Chen¹, Yinqiong Feng⁴, Hang Ma³, Wanqun Chen^4✉, Xuegang Li^3✉, Xiaoli Ye^1✉

1. Engineering Research Center of Coptis Development and Utilization (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, 400715, China.
2. Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, China.
3. School of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, 400038, China.
4. Department of Gastroenterology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400000, China.
# These authors share co-first authorship.

✉ Corresponding authors: Xiaoli Ye, Engineering Research Center of Coptis Development and Utilization (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, 400715, China; 86 023-68250728; Fax: 86 023-68250728; Email: yexia More

Citation:

Liu K, Huang H, Xiong M, Wang Q, Chen X, Feng Y, Ma H, Chen W, Li X, Ye X. IL-33 Accelerates Chronic Atrophic Gastritis through AMPK-ULK1 Axis Mediated Autolysosomal Degradation of GKN1. Int J Biol Sci 2024; 20(6):2323-2338. doi:10.7150/ijbs.93573. https://www.ijbs.com/v20p2323.htm

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Abstract

Chronic atrophic gastritis (CAG) is a complex disease characterized by atrophy and inflammation in gastric mucosal tissue, especially with high expression of interleukins. However, the interaction and mechanisms between interleukins and gastric mucosal epithelial cells in CAG remain largely elusive. Here, we elucidate that IL-33 stands out as the predominant inflammatory factor in CAG, and its expression is induced by H. pylori and MNNG through the ROS-STAT3 signaling pathway. Furthermore, our findings reveal that the IL-33/ST2 axis is intricately involved in the progression of CAG. Utilizing phosphoproteomics mass spectrometry, we demonstrate that IL-33 enhances autophagy in gastric epithelial cells through the phosphorylation of AMPK-ULK1 axis. Notably, inhibiting autophagy alleviates CAG severity, while augmentation of autophagy exacerbates the disease. Additionally, ROS scavenging emerges as a promising strategy to ameliorate CAG by reducing IL-33 expression and inhibiting autophagy. Intriguingly, IL-33 stimulation promotes GKN1 degradation through the autolysosomal pathway. Clinically, the combined measurement of IL-33 and GKN1 in serum shows potential as diagnostic markers. Our findings unveil an IL-33-AMPK-ULK1 regulatory mechanism governing GKN1 protein stability in CAG, presenting potential therapeutic targets for its treatment.

Keywords: IL-33, Autophagy, AMPK, ULK1, GKN1, Chronic Atrophic Gastritis.

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APA

Liu, K., Huang, H., Xiong, M., Wang, Q., Chen, X., Feng, Y., Ma, H., Chen, W., Li, X., Ye, X. (2024). IL-33 Accelerates Chronic Atrophic Gastritis through AMPK-ULK1 Axis Mediated Autolysosomal Degradation of GKN1. International Journal of Biological Sciences, 20(6), 2323-2338. https://doi.org/10.7150/ijbs.93573.

ACS

Liu, K.; Huang, H.; Xiong, M.; Wang, Q.; Chen, X.; Feng, Y.; Ma, H.; Chen, W.; Li, X.; Ye, X. IL-33 Accelerates Chronic Atrophic Gastritis through AMPK-ULK1 Axis Mediated Autolysosomal Degradation of GKN1. Int. J. Biol. Sci. 2024, 20 (6), 2323-2338. DOI: 10.7150/ijbs.93573.

NLM

CSE

Liu K, Huang H, Xiong M, Wang Q, Chen X, Feng Y, Ma H, Chen W, Li X, Ye X. 2024. IL-33 Accelerates Chronic Atrophic Gastritis through AMPK-ULK1 Axis Mediated Autolysosomal Degradation of GKN1. Int J Biol Sci. 20(6):2323-2338.

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