期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 527, 期 4, 页码 953-959出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.04.138
关键词
RNA demethylase; CKD; Autophagy; Uremia; Leukocytes
资金
- National Health Research Institute [NHRI-EX106-10617SI]
- National Science Council [108-2314-B-182A-135, 108-2314-B-182A134 -MY3, 105-2628-B-182009-MY4]
- Chang Gung Memorial Hospital [CMRPG3I0061, CMRPG3H0133, CMRPG3I0322, CMRPG3H0842, CORPG3K0011]
Patients with chronic kidney diseases have multiple cellular dysfunctions leading to increased atherosclerosis, impaired immunity, and disturbed metabolism. However, it is unclear what is the fundamental signaling served as a marker or as a mediator for the dysregulated function in their leukocytes or tissues. Here we hypothesized that the N-6-Methyladenosine (m(6)A) modification of the RNA in the leukocytes is responsible for the cellular dysfunction in chronic kidney diseases. Patients with chronic kidney diseases had significantly less m(6)A abundances in leukocytes and elevated RNA demethylase FTO proteins. The uremic toxin, indoxyl sulfate, activated the autophagy flux through modulation of FTO and m(6)A modifications in RNA. Notably, knockdown of FTO or inhibit the m(6)A by 3-deazaadenosine blocks the effects of indoxyl sulfate on autophagy activation in cells. These findings provide new insights into the mechanisms underlying chronic kidney disease-associated cellular dysfunction. Targeting RNA m(6)A modification may be a novel strategy for the treatment of chronic kidney diseases and autophagy. (C) 2020 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据