PMID- 36590506
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230111
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 8
IP  - 12
DP  - 2022 Dec
TI  - LOX-1 attenuates high glucose-induced autophagy via AMPK/HNF4alpha signaling in 
      HLSECs.
PG  - e12385
LID - 10.1016/j.heliyon.2022.e12385 [doi]
LID - e12385
AB  - Type 2 diabetes mellitus (T2DM) combined with nonalcoholic fatty liver disease 
      (NAFLD) is a common cause of death. Lectin-like oxidized low-density lipoprotein 
      receptor-1 (LOX-1) is involved in the regulation of autophagy and associated with 
      a variety of diseases, such as atherosclerosis, diabetes, and NAFLD. This study 
      aimed to investigate the effect of LOX-1 on autophagy induced by high glucose 
      levels in human liver sinusoidal endothelial cells (HLSECs) and whether it 
      regulates autophagy through the adenosine monophosphate-activated protein 
      kinase/hepatocyte nuclear factor 4alpha (AMPK/HNF4alpha) pathway. In this study, HLSECs 
      cultured with high glucose medium showed increased expression of LOX-1, whereas 
      autophagy was inhibited. High glucose levels decreased the AMPK phosphorylation, 
      increased the HNF4alpha phosphorylation, and retained the HNF4alpha in the cytoplasm. By 
      contrast, silencing of LOX-1 reversed the phenomenon induced by high glucose 
      levels and restored the HNF4a localization. Taken together, our findings reveal a 
      novel mechanism of high glucose-induced autophagy in HLSECs, namely, the 
      LOX-1-mediated AMPK/HNF4alpha signaling pathway. Therefore, LOX-1 is an important 
      target molecule for the regulation of autophagy in HLSECs.
CI  - (c) 2022 The Author(s).
FAU - Duan, Qidang
AU  - Duan Q
AD  - The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu 
      Provincial Hospital), Lanzhou, 730000, China.
FAU - Si, Huiling
AU  - Si H
AD  - The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu 
      Provincial Hospital), Lanzhou, 730000, China.
FAU - Tian, Limin
AU  - Tian L
AD  - Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, 730000, China.
FAU - Zhang, Na
AU  - Zhang N
AD  - The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu 
      Provincial Hospital), Lanzhou, 730000, China.
FAU - Qiu, Jumei
AU  - Qiu J
AD  - The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu 
      Provincial Hospital), Lanzhou, 730000, China.
FAU - Yu, Jing
AU  - Yu J
AD  - Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, 730000, China.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, 730000, China.
FAU - Zhang, Qi
AU  - Zhang Q
AD  - Department of Gerontology, Gansu Provincial Hospital, Lanzhou, 730000, China.
LA  - eng
PT  - Journal Article
DEP - 20221217
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC9800541
OTO - NOTNLM
OT  - AMPK
OT  - Autophagy
OT  - HLSECs
OT  - HNF4alpha
OT  - LOX-1
COIS- The authors declare no competing interests.
EDAT- 2023/01/03 06:00
MHDA- 2023/01/03 06:01
PMCR- 2022/12/17
CRDT- 2023/01/02 04:28
PHST- 2022/10/07 00:00 [received]
PHST- 2022/11/10 00:00 [revised]
PHST- 2022/12/08 00:00 [accepted]
PHST- 2023/01/02 04:28 [entrez]
PHST- 2023/01/03 06:00 [pubmed]
PHST- 2023/01/03 06:01 [medline]
PHST- 2022/12/17 00:00 [pmc-release]
AID - S2405-8440(22)03673-8 [pii]
AID - e12385 [pii]
AID - 10.1016/j.heliyon.2022.e12385 [doi]
PST - epublish
SO  - Heliyon. 2022 Dec 17;8(12):e12385. doi: 10.1016/j.heliyon.2022.e12385. 
      eCollection 2022 Dec.