BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade
Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current i...
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024031451 |
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| author | Guangyi Huang Shaoyang Zhang Jing Liao Yuanjun Qin Yiyi Hong Qi Chen Yunru Lin Yue Li Lin Lan Wen Hu Kongqian Huang Fen Tang Ningning Tang Li Jiang Chaolan Shen Ling Cui Haibin Zhong Min Li Peng Lu Qinmeng Shu Yantao Wei Fan Xu |
| author_facet | Guangyi Huang Shaoyang Zhang Jing Liao Yuanjun Qin Yiyi Hong Qi Chen Yunru Lin Yue Li Lin Lan Wen Hu Kongqian Huang Fen Tang Ningning Tang Li Jiang Chaolan Shen Ling Cui Haibin Zhong Min Li Peng Lu Qinmeng Shu Yantao Wei Fan Xu |
| author_sort | Guangyi Huang |
| collection | DOAJ |
| description | Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action. Main methods: This study utilized male and female systemic BMX knockout (BMX−/−) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level. Key findings: Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway. Significance: Our investigation showed that BMX−/− reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury. |
| first_indexed | 2024-03-07T20:03:46Z |
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| id | doaj.art-1319880ac19b478090b2661fb2434c49 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T23:14:39Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-1319880ac19b478090b2661fb2434c492024-03-17T07:57:23ZengElsevierHeliyon2405-84402024-03-01105e27114BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascadeGuangyi Huang0Shaoyang Zhang1Jing Liao2Yuanjun Qin3Yiyi Hong4Qi Chen5Yunru Lin6Yue Li7Lin Lan8Wen Hu9Kongqian Huang10Fen Tang11Ningning Tang12Li Jiang13Chaolan Shen14Ling Cui15Haibin Zhong16Min Li17Peng Lu18Qinmeng Shu19Yantao Wei20Fan Xu21Department of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaDepartment of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, ChinaEye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Key Laboratory of Myopia (Fudan University), Chinese Academy of Medical Sciences, National Health Commission, Shanghai, China; Corresponding author.State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 7 Jinsui Road, Guangzhou, 510060, China; Corresponding author.Department of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, China; Corresponding authors.Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action. Main methods: This study utilized male and female systemic BMX knockout (BMX−/−) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level. Key findings: Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway. Significance: Our investigation showed that BMX−/− reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury.http://www.sciencedirect.com/science/article/pii/S2405844024031451BMXApoptosisIschemia/reperfusionInflammationNeuroprotectionRetina |
| spellingShingle | Guangyi Huang Shaoyang Zhang Jing Liao Yuanjun Qin Yiyi Hong Qi Chen Yunru Lin Yue Li Lin Lan Wen Hu Kongqian Huang Fen Tang Ningning Tang Li Jiang Chaolan Shen Ling Cui Haibin Zhong Min Li Peng Lu Qinmeng Shu Yantao Wei Fan Xu BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade Heliyon BMX Apoptosis Ischemia/reperfusion Inflammation Neuroprotection Retina |
| title | BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade |
| title_full | BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade |
| title_fullStr | BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade |
| title_full_unstemmed | BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade |
| title_short | BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade |
| title_sort | bmx deletion mitigates neuroinflammation induced by retinal ischemia reperfusion through modulation of the akt erk stat3 signaling cascade |
| topic | BMX Apoptosis Ischemia/reperfusion Inflammation Neuroprotection Retina |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024031451 |
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