Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00151)
Name |
Spinal cord injury
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ICD |
ICD-11: ND51
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Full List of Target(s) of This Ferroptosis-centered Disease
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Drug | lipoxin A4 | Investigative | |||
Responsed Regulator | RAC-alpha serine/threonine-protein kinase (AKT1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
PI3K-Akt signaling pathway | hsa04151 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | mPSCNs (Mouse primary spinal cord neurons) | ||||
In Vivo Model |
Pregnant C57BL/6 mouse was purchased from Laboratory Animal Center of Xinxiang Medical University. pregnant mouse was anesthetized with CO2 and sacrificed by cervical dislocation at embryonic day 15. All embryos were separated from pregnant mouse under aseptic conditions. Under dissection microscope, each embryo was quickly killed by cervical dislocation, and the spinal cord was isolated. The membrane of the spinal cord and dorsal root ganglion was removed from the spinal cord applying microforceps. Subsequently, the spinal cord was quickly cut into small pieces (1 mm3) using ultrafine microscissors.
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Response regulation | Lipoxin A4 (LXA4) enhanced the protein expression of p-AKT, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and haem-oxygenase-1 (HO-1) in primary spinal cord neurons. LXA4 exerted a neuroprotective effect in Erastin-induced ferroptosis of primary spinal cord neurons by activating the Akt/Nrf2/HO-1 signaling pathway. Thus, LXA4 may be a potential therapeutic agent for spinal cord injury (SCI). | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [6] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Drug | Carnosic acid | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | PC12 cells | Adrenal gland pheochromocytoma | Rattus norvegicus | CVCL_0481 | |
Response regulation | Ferroptosis is involved in the pathogenesis of spinal cord injury (SCI). Carnosic acid (CA) is a natural phenolic diterpene, which possesses diversiform activities. CA can inhibit ferroptosis in PC12 cells induced by erastin via activating Nrf2 pathway, indicating that CA could lead to neuroprotective effect by restraining the occurrence of ferroptosis. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Regulator | Growth/differentiation factor 15 (GDF15) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | rPNs (Rat primary neurons) | ||||
In Vivo Model |
Total of 50 C57BL/6J adult mice (males, average weight of 20 g, 8 weeks of age) were acquired from Charles River (Beijing, China). In brief, ketamine (80 mg/kg) was utilized to anesthetize mice before the skin was prepared for disinfection, and then the back skin was incised to expose the lamina at T10. Finally, a moderate contusion (5 g x 5 cm) was created by an impactor (RWD, Shenzhen, China). Spinal cord hemorrhage, hindlimb extension, and delayed paralysis suggest successful modeling. Only laminectomy was performed in the Sham group.
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Response regulation | GDF15 effectively alleviated neuronal ferroptosis post spinal cord injury (SCI) via the p62-Keap1-Nrf2 signaling pathway and promoted locomotor recovery of SCI mice, which is suggested as a potential target on SCI pathogenesis and treatment. | ||||
Unspecific Target
In total 4 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Drug | Astragaloside IV | Investigative | |||
Responsed Regulator | Transcription factor EB (TFEB) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
In Vitro Model | PC12 cells | Adrenal gland pheochromocytoma | Rattus norvegicus | CVCL_0481 | |
Response regulation | Astragaloside IV markedly accelerated proliferation, suppressed apoptosis, and reduced ROS and LDH accumulation. Furthermore, AS-IV enhanced TFEB expression in H2O2-damaged PC12 cells. The effects of AS-IV on spinal cord injury were inhibited by si-TFEB, and this inhibition was further reinforced by the addition of FIN56.The results of this investigation using the SCI cell model suggested that AS-IV alleviated SCI by promoting TFEB expression and subsequently mediating ferroptosis. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Drug | Epigallocatechin Gallate | Investigative | |||
Responsed Regulator | Polycystin-1 (PKD1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | rCGNs (Rat cerebellar granule neurons) | ||||
Response regulation | (-)-Epigallocatechin-3-gallate (EGCG) upregulated PKD1 phosphorylation levels and inhibited ferroptosis to reduce the cell death of CGNs under oxidative stress and to promote functional recovery and ERK phosphorylation in rats following complete ST. Together, EGCG is a novel strategy for the treatment of spinal cord injury (SCI) related to PKD1 phosphorylation and ferroptosis. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [12] | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Drug | Proanthocyanidin | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | mSCs (Mouse splenocytes) | ||||
In Vivo Model |
Female C57BL/6 mice (10-12 weeks old, weighing 24-26 g) were used in this study. Mice were randomly assigned to the following groups: (1) Sham group, subjected to laminectomy operation; (2) SCI group, which underwent SCI with intraperitoneal injection (i.p.) of saline; (3) PACs5 group (5 mg/kg PACs), which underwent SCI with i.p. of 5 mg/kg PACs solved in saline; (4) PACs10 group (10 mg/kg PACs), which underwent SCI with i.p. of 10 mg/kg PACs solutions.
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Response regulation | Proanthocyanidins (PACs) treatment significantly decreased the levels of iron, TBARS, ACSL4, and Alox15B, while increased the levels of GSH, GPX4, Nrf2, and HO-1 in traumatic spinal cords. Above all, PACs improved the locomotive function of spinal cord injury (SCI) mice. These results suggest that PACs might be potential therapeutics for SCI repair by inhibiting ferroptosis in SCI. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [13] | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Drug | SRS 16-86 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | rSCs (Rat spinal cords) | ||||
In Vivo Model |
Female Wistar rats (n = 120) weighing 240 ± 10 g were purchased from Laboratory Animal Center of the Academy of Military Medical Sciences (Beijing, China). To optimize the SRS 16-86 dose, 20 animals were divided into five groups to test the locomotor recovery at 2 weeks after SCI (n = 4 per group, Sham, SCI-vehicle, 5 mg/kg, 10 mg/kg and 15 mg/kg of SRS 16-86 intraperitoneally). According to the two week preliminary experiments, the dose of 15 mg/kg SRS 16-86 was used in the following experiments. For the TEM observation, 15 animals were divided into five groups (n = 3, Sham, SCI-15min, SCI-1 h, SCI 4 h and SCI 24 h to see the mitochondria changes. Another 9 animals were assigned to detect the TEM of spinal cord at 24 h post injury (n = 3 per group, Sham, SCI-vehicle and SCI-SRS 16-86). 18 animals were used (n = 6 per group, Sham, SCI-vehicle and SCI-SRS 16-86) to observe the hindlimb function at 1 d, 7 d, 14 d, 28 d, 42 d and 56 d after SCI.
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Response regulation | SRS 16-86 treatment alleviated astrogliosis and enhanced neuronal survival after spinal cord injury (SCI). The inflammatory cytokine levels (IL-1, TNF- and ICAM-1) were decreased significantly post SRS 16-86 treatment after SCI. These findings suggest strong correlation between ferroptosis and the secondary injury of SCI. | ||||
Polyunsaturated fatty acid lipoxygenase ALOX15 (ALOX15)
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Regulator | Dihydroorotate dehydrogenase (quinone), mitochondrial (DHODH) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | PC12 cells | Adrenal gland pheochromocytoma | Rattus norvegicus | CVCL_0481 | |
In Vivo Model |
Forty female Sprague-Dawley rats (200-300 g, 8 weeks old) were purchased from the Animal Experiment Center of Fudan University. Forty rats were randomly divided into four groups: sham operation group (n = 10), SCI group (n = 10), SCI + ferroptosis inhibitor group (SCI + ferrostatin1) (n = 10), and SCI + DHODH Inhibitor group (SCI + teriflunomide) (n = 10). Ten rats in the sham group only received laminectomy without SCI. To induce spinal cord injury, spinal cord injury surgery was performed in the middle thoracic region of rats (T8-T9).
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Response regulation | The application of DHODH is a potential treatment for spinal cord injury (SCI). DHODH can reduce the ferroptosis of neurons after spinal cord injury by regulating the P53/ALOX15 signaling pathway, thereby alleviating spinal cord injury. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Regulator | Dihydroorotate dehydrogenase (quinone), mitochondrial (DHODH) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | PC12 cells | Adrenal gland pheochromocytoma | Rattus norvegicus | CVCL_0481 | |
In Vivo Model |
Forty female Sprague-Dawley rats (200-300 g, 8 weeks old) were purchased from the Animal Experiment Center of Fudan University. Forty rats were randomly divided into four groups: sham operation group (n = 10), SCI group (n = 10), SCI + ferroptosis inhibitor group (SCI + ferrostatin1) (n = 10), and SCI + DHODH Inhibitor group (SCI + teriflunomide) (n = 10). Ten rats in the sham group only received laminectomy without SCI. To induce spinal cord injury, spinal cord injury surgery was performed in the middle thoracic region of rats (T8-T9).
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Response regulation | The application of DHODH is a potential treatment for spinal cord injury (SCI). DHODH can reduce the ferroptosis of neurons after spinal cord injury by regulating the P53/ALOX15 signaling pathway, thereby alleviating spinal cord injury. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | PC12 cells | Adrenal gland pheochromocytoma | Rattus norvegicus | CVCL_0481 | |
In Vivo Model |
Forty female Sprague-Dawley rats (200-300 g, 8 weeks old) were purchased from the Animal Experiment Center of Fudan University. Forty rats were randomly divided into four groups: sham operation group (n = 10), SCI group (n = 10), SCI + ferroptosis inhibitor group (SCI + ferrostatin1) (n = 10), and SCI + DHODH Inhibitor group (SCI + teriflunomide) (n = 10). Ten rats in the sham group only received laminectomy without SCI. To induce spinal cord injury, spinal cord injury surgery was performed in the middle thoracic region of rats (T8-T9).
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Response regulation | The application of DHODH is a potential treatment for spinal cord injury (SCI). DHODH can reduce the ferroptosis of neurons after spinal cord injury by regulating the P53/ALOX15 signaling pathway, thereby alleviating spinal cord injury. | ||||
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Drug | Edaravone | Approved | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | rSCTs (Rat spinal cord tissues) | ||||
In Vivo Model |
The rats were initially anesthetized with 5% isoflurane (RWD life science, Shenzhen, China) and then maintained with 22.5% isoflurane. A 1-cm midline incision was made over the thoracic vertebrae, and laminectomy on T10 and the caudal half of T9 vertebrae was performed. Spinal cord contusion injury was conducted by NYU Impactor Model III (W.M. Keck Center for Collaborative Neuroscience Rutgers, The State University of New Jersey, United States) using a 10-g node dropping freely from a height of 2.5 cm and muscles and skin sutured in layers. Sham controls underwent laminectomy without the contusion. To prevent infection at the incision, cefuroxime sodium was applied for 3 days after injury. The bladders were emptied manually twice daily in the first week after injury.
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Response regulation | Edaravone not only rescues the ferroptosis negative regulators, xCT and GPX4, but also downregulates those pro-ferroptosis factors, ACSL4 and 5-LOX. Therefore, secondary injury below the lesion site is reversed by edaravone via ferroptosis inhibition. And in the acute phase of spinal cord injury (SCI), edaravone reduced neuronal cell death and neuroinflammation. | ||||
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Drug | Edaravone | Approved | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | rSCTs (Rat spinal cord tissues) | ||||
In Vivo Model |
The rats were initially anesthetized with 5% isoflurane (RWD life science, Shenzhen, China) and then maintained with 22.5% isoflurane. A 1-cm midline incision was made over the thoracic vertebrae, and laminectomy on T10 and the caudal half of T9 vertebrae was performed. Spinal cord contusion injury was conducted by NYU Impactor Model III (W.M. Keck Center for Collaborative Neuroscience Rutgers, The State University of New Jersey, United States) using a 10-g node dropping freely from a height of 2.5 cm and muscles and skin sutured in layers. Sham controls underwent laminectomy without the contusion. To prevent infection at the incision, cefuroxime sodium was applied for 3 days after injury. The bladders were emptied manually twice daily in the first week after injury.
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Response regulation | Edaravone not only rescues the ferroptosis negative regulators, xCT and GPX4, but also downregulates those pro-ferroptosis factors, ACSL4 and 5-LOX. Therefore, secondary injury below the lesion site is reversed by edaravone via ferroptosis inhibition. And in the acute phase of spinal cord injury (SCI), edaravone reduced neuronal cell death and neuroinflammation. | ||||
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Drug | Edaravone | Approved | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | rSCTs (Rat spinal cord tissues) | ||||
In Vivo Model |
The rats were initially anesthetized with 5% isoflurane (RWD life science, Shenzhen, China) and then maintained with 22.5% isoflurane. A 1-cm midline incision was made over the thoracic vertebrae, and laminectomy on T10 and the caudal half of T9 vertebrae was performed. Spinal cord contusion injury was conducted by NYU Impactor Model III (W.M. Keck Center for Collaborative Neuroscience Rutgers, The State University of New Jersey, United States) using a 10-g node dropping freely from a height of 2.5 cm and muscles and skin sutured in layers. Sham controls underwent laminectomy without the contusion. To prevent infection at the incision, cefuroxime sodium was applied for 3 days after injury. The bladders were emptied manually twice daily in the first week after injury.
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Response regulation | Edaravone not only rescues the ferroptosis negative regulators, xCT and GPX4, but also downregulates those pro-ferroptosis factors, ACSL4 and 5-LOX. Therefore, secondary injury below the lesion site is reversed by edaravone via ferroptosis inhibition. And in the acute phase of spinal cord injury (SCI), edaravone reduced neuronal cell death and neuroinflammation. | ||||
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Driver/Suppressor | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Regulator | Ubiquitin carboxyl-terminal hydrolase 7 (USP7) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | rSCs (Rat spinal cords) | ||||
In Vivo Model |
Forty-eight adult female Sprague-Dawley rats weighing 200-220 g were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Hunan, China) and divided into the following eight groups: sham (n = 6), SCI (n = 6), SCI + lentivirus (LV)-negative control 1 (NC1) (n = 6), SCI + LV-HMOX-1 (n = 6), SCI + LV-NC2 (n = 6), SCI + LV-USP7 (n = 6), SCI + LV-USP7 + sh-NC (n = 6), and SCI + LV-USP7 + sh-HMOX-1 (n = 6) groups. One week after animal adaptation and 30 min before operation, a subcutaneous injection of buprenorphine (0.05 mg/kg) was administered to the rats, along with inhalation of 5% isoflurane and an intraperitoneal injection of ketamine (75 mg/kg) and thiazide (10 mg/kg).
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Response regulation | In spinal cord injury (SCI) rats, USP7 directly bound to HMOX-1 and its overexpression promoted HMOX-1 expression via deubiquitination. To sum up, USP7 overexpression facilitated the expression of HMOX-1 through deubiquitination, thereby reducing ferroptosis and alleviating SCI. | ||||
Ferroptosis suppressor protein 1 (AIFM2)
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [9] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Regulator | rno-miR-672-3p (miRNA) | Driver | |||
Pathway Response | Glutathione metabolism | hsa00480 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | AGE1.HN cells | Normal | Homo sapiens | CVCL_DF60 | |
PC12 cells | Adrenal gland pheochromocytoma | Rattus norvegicus | CVCL_0481 | ||
In Vivo Model |
Adult male Sprague-Dawley rats weighing 200-220 g were purchased from the Animal Center of the Medical Department of Xi'an Jiaotong University. The rats were anesthetized by intraperitoneal injection of 1% pentobarbital sodium (50 mg/kg), and the spines of the rats were fixed. The skin of T9-12 level was incised, and laminectomy was performed at the T10 level to expose the spinal cord. The rats were then placed in the appropriate position of the impactor so that 10 g of rod fell freely at a height of 3 cm and hit the center of the T10 level of the spinal cord. The signs of successful establishment of the model were the appearance of hind limb extension and tail-flick reflex in rats. Laminectomy was performed only in the sham-operated group. The rats in the SCI group received an artificial bladder massage twice a day to assist in urination until they were able to urinate.
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Response regulation | miR-672-3p exerts a neural restoration effectin vivo and in vitro by inhibiting ferroptosis via the FSP1 pathway. In addition, miR-672-3p improved locomotor function in spinal cord injury rats, suggesting its potential as a target for the development of therapeutics for SCI. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [10] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Acute spinal cord injury [ICD-11: ND51] | ||||
Responsed Regulator | lncGm36569 (IncRNA) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | HT22 cells | Normal | Mus musculus | CVCL_0321 | |
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
Male C57BL/6 (7-8 weeks) were purchased from the Animal Center of Nanjing University (Nanjing, China) and housed in the condition with controlled temperature and humidity under a 12-h light/dark circadian rhythm. For determining the effects of MSCs-exo, the animals were derived into three groups: sham (n = 10), ASCI (n = 10), ASCI + MSCs (n = 10); for determining the effects of exosomal lncGm36569, the animals were divided into five groups: sham (n = 10), ASCI (n = 10), ASCI + MSC-Exo (ctrl) (n = 10), ASCI + MSCs-Exo (lnc-OE) (n =10), ASCI + MSCs-Exo (si-lnc) (n = 10).
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Response regulation | Exosomes derived from mesenchymal stem cells (MSCs) have been considered as an alternative for cell therapy of acute spinal cord injury (ASCI). MSCs-exosomes lncGm36569 inhibited neuronal cell ferroptosis through miR-5627-5p/FSP1 axis, thereby attenuating neuronal dysfunction. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [10] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Acute spinal cord injury [ICD-11: ND51] | ||||
Responsed Regulator | mmu-miR-5627-5p (miRNA) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | HT22 cells | Normal | Mus musculus | CVCL_0321 | |
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
Male C57BL/6 (7-8 weeks) were purchased from the Animal Center of Nanjing University (Nanjing, China) and housed in the condition with controlled temperature and humidity under a 12-h light/dark circadian rhythm. For determining the effects of MSCs-exo, the animals were derived into three groups: sham (n = 10), ASCI (n = 10), ASCI + MSCs (n = 10); for determining the effects of exosomal lncGm36569, the animals were divided into five groups: sham (n = 10), ASCI (n = 10), ASCI + MSC-Exo (ctrl) (n = 10), ASCI + MSCs-Exo (lnc-OE) (n =10), ASCI + MSCs-Exo (si-lnc) (n = 10).
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Response regulation | Exosomes derived from mesenchymal stem cells (MSCs) have been considered as an alternative for cell therapy of acute spinal cord injury (ASCI). MSCs-exosomes lncGm36569 inhibited neuronal cell ferroptosis through miR-5627-5p/FSP1 axis, thereby attenuating neuronal dysfunction. | ||||
Beclin-1 (BECN1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [11] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Spinal cord injury [ICD-11: ND51] | ||||
Responsed Regulator | Ubiquitin carboxyl-terminal hydrolase 11 (USP11) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | |
In Vivo Model |
The mouse SCIRI model was established in 6- to 8-week-old C57BL/6 male mice. Mice were anesthetized by isoflurane inhalation and fixed in a supine position, and a midline abdominal incision method was used. After positioning of the left kidney through the peritoneum, we carefully searched for and separated the abdominal aorta along the left renal artery. The abdominal aorta was clamped under the exit of the left renal artery (which was not clamped in sham-operated mice). After 60 min, the aneurysm clip was removed and blood perfusion was restored. After the operation, the mice were placed in a cage alone and kept warm, and the bladder was massaged once every 8 h until the bladder reflex was restored.
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Response regulation | USP11 plays a key role in regulating ferroptosis and additionally identifies USP11-mediated autophagy-dependent ferroptosis as a promising target for the treatment of spinal cord ischemia-reperfusion injury (SCIRI). USP11 promotes autophagy activation by stabilizing Beclin 1, thereby leading to ferroptosis. | ||||
References