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Endoplasmic reticulum stress increases LECT2 expression via ATF4

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Abstract
Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity, insulin resistance, and
endoplasmic reticulum (ER) stress. Elevated circulating levels of the hepatokine leukocyte cell-derived
chemotaxin-2 (LECT2) have also been noted in NAFLD; however, the mechanism underlying this association
is unclear. To investigate a possible link between ER stress/unfolded protein response (UPR)
signaling and LECT2 secretion, HepG2 cells were incubated with ER stress inducers with or without an ER
stress-reducing chemical chaperone. Additionally, UPR pathway genes were knocked down and overexpressed,
and a ChIP assay was performed. In diet-induced obese mice, hepatic expression of LECT2 and
activating transcription factor 4 (ATF4) was measured. In HepG2 cells, LECT2 expression was increased by
ER stressors, an effect blocked by the chemical chaperone. Among UPR pathway proteins, only knockdown
of ATF4 suppressed ER stress-induced LECT2 expression, while overexpression of ATF4 enhanced
LECT2 expression. The ChIP assay revealed that ATF4 binds to three putative binding sites on the LECT2
promoter and binding is promoted by an ER stress inducer. In steatotic livers of obese mice, LECT2 and
ATF4 expression was concomitantly elevated. Our data indicate that activation of ER stress/UPR signaling
induces LECT2 expression in steatotic liver; specifically, ATF4 appears to mediate upregulation of LECT2
transcription.
Author(s)
김동욱김지민박찬윤박혜순이슬기장연진정지훈최경철최한석한성림
Issued Date
2021
Type
Article
Keyword
ATF4ER stressHepatokineLECT2NAFLDObesity
DOI
10.1016/j.bbrc.2021.11.038
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8323
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2601480242&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Endoplasmic%20reticulum%20stress%20increases%20LECT2%20expression%20via%20ATF4&offset=0&pcAvailability=true
Publisher
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Location
미국
Language
영어
ISSN
0006-291X
Citation Volume
585
Citation Number
1
Citation Start Page
169
Citation End Page
171
Appears in Collections:
Medicine > Medicine
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