MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4
Renal ischemia is the initial stage of kidney damage, leading to mitochondrial metabolism disorders and cell necrosis. In this study, we aimed to investigate the biological functions and potential mechanisms of miR-21 in protecting renal tubular epithelial cells from oxidative stress and apoptosis f...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023030256 |
| _version_ | 1797815636766752768 |
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| author | Xiu-Juan Liu Jin-Lei Lv Xin Zou Yan-Yan Yu Hong-Xia Zhou Yu Wu Yan-Qiu Geng Cai-Hua Lie |
| author_facet | Xiu-Juan Liu Jin-Lei Lv Xin Zou Yan-Yan Yu Hong-Xia Zhou Yu Wu Yan-Qiu Geng Cai-Hua Lie |
| author_sort | Xiu-Juan Liu |
| collection | DOAJ |
| description | Renal ischemia is the initial stage of kidney damage, leading to mitochondrial metabolism disorders and cell necrosis. In this study, we aimed to investigate the biological functions and potential mechanisms of miR-21 in protecting renal tubular epithelial cells from oxidative stress and apoptosis following oxygen glucose deprivation (OGD). Following an OGD injury, miR-21 levels increased in HK-2 renal tubular epithelial cells. Overexpression of miR-21 decreased the protein expressions of cleaved caspase-3, BAX, P53, cell apoptosis and increased Bcl-2 expression in HK-2 cells with OGD injury. In vivo studies found that miR-21 agomir reduced renal tissue apoptosis, while miR-21 antagomir increased it. In addition, overexpression of miR-21 reduced levels of reactive oxygen species (ROS), malondialdehyde (MDA) and lactate dehydrogenase (LDH) in HK-2 cells with OGD injury. However, miR-21 inhibition exhibited the opposite effect. A dual-luciferase reporter assay demonstrated that miR-21 directly regulates Toll-like receptor 4 (TLR4) by targeting the 3′-UTR of TLR4 mRNA. Overexpression of miR-21 led to decreased TLR4 protein expression, and TLR4 knockdown was shown to greatly increase AKT activity in HK-2 cells by in vitro kinase assay. Additionally, TLR4 knockdown promoted AKT phosphorylation and hypoxia-inducible factor-1α (HIF-1α) expression, while TLR4 overexpression inhibited these processes. Furthermore, AKT activation abolished the effect of TLR4 on HIF-1α, while AKT inhibition decreased the expression of TLR4 on HIF-1α in TLR4 knockdown HK-2 cells. Further study revealed that HIF-1α inhibition abolished the protective effect of miR-21 overexpression on ROS, LDH levels and cell apoptosis in HK-2 cells after OGD injury, which is indicated by increased levels of ROS and LDH, as well as increased cell apoptosis after HIF-1α inhibition in miR-21-treated HK-2 cells. In conclusion, miR-21 defends OGD-induced HK-2 cell injury via the TLR4/AKT/HIF-1α axis. |
| first_indexed | 2024-03-13T08:25:48Z |
| format | Article |
| id | doaj.art-75127c9562a74e4eb3f8d1f5bc31d7fb |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-13T08:25:48Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-75127c9562a74e4eb3f8d1f5bc31d7fb2023-05-31T04:45:39ZengElsevierHeliyon2405-84402023-05-0195e15818MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4Xiu-Juan Liu0Jin-Lei Lv1Xin Zou2Yan-Yan Yu3Hong-Xia Zhou4Yu Wu5Yan-Qiu Geng6Cai-Hua Lie7Division of Nephrology, The 908 Hospital of Joint Logistics Support Force, Nanchang, Jiangxi, 330000, ChinaDepartment of Nephrology, The First Affiliated Hospital of Nanchang University, Institute of Molecular Immunology of Kidney Disease of Nanchang University, Nanchang, Jiangxi, 330006, ChinaDivision of Nephrology, The 908 Hospital of Joint Logistics Support Force, Nanchang, Jiangxi, 330000, ChinaDivision of Nephrology, The 908 Hospital of Joint Logistics Support Force, Nanchang, Jiangxi, 330000, ChinaDivision of Nephrology, The 908 Hospital of Joint Logistics Support Force, Nanchang, Jiangxi, 330000, ChinaDivision of Nephrology, The 908 Hospital of Joint Logistics Support Force, Nanchang, Jiangxi, 330000, ChinaDivision of Nephrology, Third Medical Center of Chinese PLA General Hospital, Beijing, 100039, China; Corresponding author. Division of Nephrology, Third Medical Center of Chinese PLA General Hospital, 69 Yongding Road, Beijing, 100039, China.Division of Nephrology, General Hospital of Xinjiang Military Region, Urumqi, Xinjiang, 830000, China; Corresponding author. Division of Nephrology, General Hospital of Xinjiang Military Region, 359 Youhaobei Road, Urumqi, Xinjiang, 830000, China.Renal ischemia is the initial stage of kidney damage, leading to mitochondrial metabolism disorders and cell necrosis. In this study, we aimed to investigate the biological functions and potential mechanisms of miR-21 in protecting renal tubular epithelial cells from oxidative stress and apoptosis following oxygen glucose deprivation (OGD). Following an OGD injury, miR-21 levels increased in HK-2 renal tubular epithelial cells. Overexpression of miR-21 decreased the protein expressions of cleaved caspase-3, BAX, P53, cell apoptosis and increased Bcl-2 expression in HK-2 cells with OGD injury. In vivo studies found that miR-21 agomir reduced renal tissue apoptosis, while miR-21 antagomir increased it. In addition, overexpression of miR-21 reduced levels of reactive oxygen species (ROS), malondialdehyde (MDA) and lactate dehydrogenase (LDH) in HK-2 cells with OGD injury. However, miR-21 inhibition exhibited the opposite effect. A dual-luciferase reporter assay demonstrated that miR-21 directly regulates Toll-like receptor 4 (TLR4) by targeting the 3′-UTR of TLR4 mRNA. Overexpression of miR-21 led to decreased TLR4 protein expression, and TLR4 knockdown was shown to greatly increase AKT activity in HK-2 cells by in vitro kinase assay. Additionally, TLR4 knockdown promoted AKT phosphorylation and hypoxia-inducible factor-1α (HIF-1α) expression, while TLR4 overexpression inhibited these processes. Furthermore, AKT activation abolished the effect of TLR4 on HIF-1α, while AKT inhibition decreased the expression of TLR4 on HIF-1α in TLR4 knockdown HK-2 cells. Further study revealed that HIF-1α inhibition abolished the protective effect of miR-21 overexpression on ROS, LDH levels and cell apoptosis in HK-2 cells after OGD injury, which is indicated by increased levels of ROS and LDH, as well as increased cell apoptosis after HIF-1α inhibition in miR-21-treated HK-2 cells. In conclusion, miR-21 defends OGD-induced HK-2 cell injury via the TLR4/AKT/HIF-1α axis.http://www.sciencedirect.com/science/article/pii/S2405844023030256miR-21TLR4AKTIschemiaRenalHIF-1α |
| spellingShingle | Xiu-Juan Liu Jin-Lei Lv Xin Zou Yan-Yan Yu Hong-Xia Zhou Yu Wu Yan-Qiu Geng Cai-Hua Lie MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4 Heliyon miR-21 TLR4 AKT Ischemia Renal HIF-1α |
| title | MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4 |
| title_full | MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4 |
| title_fullStr | MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4 |
| title_full_unstemmed | MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4 |
| title_short | MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4 |
| title_sort | mir 21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting tlr4 |
| topic | miR-21 TLR4 AKT Ischemia Renal HIF-1α |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023030256 |
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