LOX-1 attenuates high glucose-induced autophagy via AMPK/HNF4α signaling in HLSECs
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,...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022036738 |
| _version_ | 1797960787229147136 |
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| author | Qidang Duan Huiling Si Limin Tian Na Zhang Jumei Qiu Jing Yu Jing Liu Qi Zhang |
| author_facet | Qidang Duan Huiling Si Limin Tian Na Zhang Jumei Qiu Jing Yu Jing Liu Qi Zhang |
| author_sort | Qidang Duan |
| collection | DOAJ |
| description | 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 4α (AMPK/HNF4α) 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 HNF4α phosphorylation, and retained the HNF4α 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/HNF4α signaling pathway. Therefore, LOX-1 is an important target molecule for the regulation of autophagy in HLSECs. |
| first_indexed | 2024-04-11T00:50:46Z |
| format | Article |
| id | doaj.art-120327b5b9d3475bb5e46763e6d93152 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-11T00:50:46Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-120327b5b9d3475bb5e46763e6d931522023-01-05T08:40:13ZengElsevierHeliyon2405-84402022-12-01812e12385LOX-1 attenuates high glucose-induced autophagy via AMPK/HNF4α signaling in HLSECsQidang Duan0Huiling Si1Limin Tian2Na Zhang3Jumei Qiu4Jing Yu5Jing Liu6Qi Zhang7The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, 730000, ChinaThe First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, 730000, ChinaDepartment of Endocrinology, Gansu Provincial Hospital, Lanzhou, 730000, ChinaThe First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, 730000, ChinaThe First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, 730000, ChinaDepartment of Endocrinology, Gansu Provincial Hospital, Lanzhou, 730000, ChinaDepartment of Endocrinology, Gansu Provincial Hospital, Lanzhou, 730000, China; Corresponding author.Department of Gerontology, Gansu Provincial Hospital, Lanzhou, 730000, China; Corresponding author.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 4α (AMPK/HNF4α) 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 HNF4α phosphorylation, and retained the HNF4α 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/HNF4α signaling pathway. Therefore, LOX-1 is an important target molecule for the regulation of autophagy in HLSECs.http://www.sciencedirect.com/science/article/pii/S2405844022036738LOX-1AutophagyHLSECsAMPKHNF4α |
| spellingShingle | Qidang Duan Huiling Si Limin Tian Na Zhang Jumei Qiu Jing Yu Jing Liu Qi Zhang LOX-1 attenuates high glucose-induced autophagy via AMPK/HNF4α signaling in HLSECs Heliyon LOX-1 Autophagy HLSECs AMPK HNF4α |
| title | LOX-1 attenuates high glucose-induced autophagy via AMPK/HNF4α signaling in HLSECs |
| title_full | LOX-1 attenuates high glucose-induced autophagy via AMPK/HNF4α signaling in HLSECs |
| title_fullStr | LOX-1 attenuates high glucose-induced autophagy via AMPK/HNF4α signaling in HLSECs |
| title_full_unstemmed | LOX-1 attenuates high glucose-induced autophagy via AMPK/HNF4α signaling in HLSECs |
| title_short | LOX-1 attenuates high glucose-induced autophagy via AMPK/HNF4α signaling in HLSECs |
| title_sort | lox 1 attenuates high glucose induced autophagy via ampk hnf4α signaling in hlsecs |
| topic | LOX-1 Autophagy HLSECs AMPK HNF4α |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022036738 |
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