DrosophilaPEBP1 inhibits intestinal stem cell aging via suppression of ERK pathway

التفاصيل البيبلوغرافية
العنوان: DrosophilaPEBP1 inhibits intestinal stem cell aging via suppression of ERK pathway
المؤلفون: Mi-Ae Yoo, Ho-Jun Jeon, Joung-Sun Park, Hae Young Chung, Jae-Sun Lee, Jung-Hoon Pyo
المصدر: Oncotarget
بيانات النشر: Impact Journals, LLC, 2018.
سنة النشر: 2018
مصطلحات موضوعية: ERK suppressor, 0301 basic medicine, MAPK/ERK pathway, intestinal stem cell, medicine.disease_cause, digestive system, PEBP1, 03 medical and health sciences, Research Paper: Gerotarget (Focus on Aging), Downregulation and upregulation, Extracellular, medicine, stem cell aging, Epidermal growth factor receptor, education, education.field_of_study, biology, Gerotarget, Kinase, Chemistry, fungi, Cell biology, 030104 developmental biology, Phosphatidylethanolamine binding protein 1, Oncology, biology.protein, Drosophila, Stem cell, Oxidative stress
الوصف: 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.
تدمد: 1949-2553
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::855d799c3c3c075171a98274c36ff4f8
https://doi.org/10.18632/oncotarget.24834
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....855d799c3c3c075171a98274c36ff4f8
قاعدة البيانات: OpenAIRE