Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Drosophila PEBP1 inhibits intestinal stem cell aging via suppression of ERK pathway

Jung-Hoon Pyo, Ho-Jun Jeon, Joung-Sun Park, Jae-Sun Lee, Hae-Young Chung and Mi-Ae Yoo _

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Oncotarget. 2018; 9:17980-17993. https://doi.org/10.18632/oncotarget.24834

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Abstract

Jung-Hoon Pyo1,2,3, Ho-Jun Jeon1, Joung-Sun Park1,2, Jae-Sun Lee4, Hae-Young Chung3 and Mi-Ae Yoo1,2

1Department of Molecular Biology, Pusan National University, Busan, Republic of Korea

2Institute of Systems Biology (ISB), Pusan National University, Busan, Republic of Korea

3Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, Republic of Korea

4Department of Molecular Medicine and Hypoxia-Related Disease Research Center, Inha University College of Medicine, Incheon, Republic of Korea

Correspondence to:

Mi-Ae Yoo, email: mayoo@pusan.ac.kr

Hae-Young Chung, email: hyjung@pusan.ac.kr

Keywords: Drosophila; intestinal stem cell; stem cell aging; PEBP1; ERK suppressor; Gerotarget

Received: November 03, 2017     Accepted: March 06, 2018     Published: April 06, 2018

ABSTRACT

The intestine is a high cellular turnover tissue largely dependent on the regenerative function of stem cell throughout life, and a signaling center for the health and viability of organisms. Therefore, better understanding of the mechanisms underlying the regulation of intestinal stem cell (ISC) regenerative potential is essential for the possible intervention of aging process and age-related diseases. Drosophila midgut is a well-established model system for studying the mechanisms underlying ISC regenerative potential during aging. Here, we report the requirement of Drosophila phosphatidylethanolamine binding protein 1 (PEBP1) in ISC regenerative potential. We showed that PEBP1 was strongly expressed in enterocytes (ECs) of guts and its decrease with age and oxidative stress. Furthermore, the downregulation of PEBP1 in ECs accelerates ISC aging, as evidenced by ISC hyper-proliferation, γH2AX accumulation, and centrosome amplification, and intestinal hyperplasia. The decrease in PEBP1 expression was associated with increased extracellular signal-regulated kinase (ERK) activity in ECs. All these phenotypes by EC-specific depletion of PEBP1 were rescued by the concomitant inhibition of ERK signaling. Our findings evidence that the age-related downregulation of PEBP1 in ECs is a novel cause accelerating ISC aging and that PEBP1 is an EC-intrinsic suppressor of epidermal growth factor receptor (EGFR)/ERK signaling. Our study provides molecular insights into the tight regulation of EGFR/ERK signaling in niches for stem cell regenerative potential.


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