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Hepatic stellate cells are activated and avoid death under necroptosis stimuli:

Title
Hepatic stellate cells are activated and avoid death under necroptosis stimuli:
Author
오주희
Alternative Author(s)
오주희
Advisor(s)
Dae Won Jun
Issue Date
2022. 2
Publisher
한양대학교
Degree
Doctor
Abstract
Background: Necroptosis is an emerging cell death pathway that allows cells to undergo “cellular suicide” in a caspase-independent manner. We investigated how hepatic stellate cells are activated and avoid death under necroptotic stimuli. Methods: Necroptosis was induced by tumor necrosis factor-α, pan-caspase inhibitors, and inhibitor of apoptosis protein inhibitors in HT-29 (colorectal cancer cells), U937 (monocytes), and LX-2 (hepatic stellate cells). LX-2 cell activation and death were evaluated after necroptosis with and without the MLKL inhibitor (necrosulfonamide). Results: Necroptotic stimuli caused death of HT-29 and U937 cells. LX-2 cells underwent activation but not cell membrane permeabilization or death upon induction of necroptosis. Necroptosis inhibitors attenuated LX-2 cell activation during necroptosis. Unlike HT-29 and U937, MLKL phosphorylation and oligomerization were not observed during necroptosis in LX-2 cells. Ribonucleic acid sequencing data showed that NF-κB signaling-related genes were increased in LX-2 cells after necroptosis stimuli. Stimulation of necroptosis in LX-2 cells increased nuclear expression of p-IκB and NF-κB, which decreased after necrosulfonamide treatment. Induction of necroptosis in LX-2 cells led to activation and autophagosome formation, attenuated by necrosulfonamide treatment. Conclusion: Hepatic stellate cells avoid necroptosis due to problems with MLKL phosphorylation and oligomerization formation and are activated via the increased NF-κB pathway and autophagosomes. Therefore, we propose that MLKL is a potential novel therapeutic strategy for liver fibrosis.
URI
http://hanyang.dcollection.net/common/orgView/200000589738https://repository.hanyang.ac.kr/handle/20.500.11754/167710
Appears in Collections:
GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > TRANSLATIONAL MEDICAL SCIENCE(임상의과학과) > Theses (Ph.D.)
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