BMP4 aggravates mitochondrial dysfunction of HRMECs

Yong Wang; Hui Li; Jingjing Cao; Aihua Liu; Zhenyu Kou; Weiting An; Jingli Liang; Xiaomin Zhang; Xiaorong Li; Lijie Dong

doi:10.1016/j.heliyon.2023.e13824

BMP4 aggravates mitochondrial dysfunction of HRMECs

Heliyon. 2023 Feb 18;9(3):e13824. doi: 10.1016/j.heliyon.2023.e13824. eCollection 2023 Mar.

Authors

Yong Wang^{1

2

3

4}, Hui Li^{1

2

3

4}, Jingjing Cao^{1

2

3

4}, Aihua Liu^{1

2

3

4}, Zhenyu Kou^{1

2

3

4}, Weiting An^{1

2

3

4}, Jingli Liang^{1

2

3

4}, Xiaomin Zhang^{1

2

3

4}, Xiaorong Li^{1

2

3

4}, Lijie Dong^{1

2

3

4}

Affiliations

¹ Tianjin Key Laboratory of Retinal Functions and Diseases, PR China.
² Tianjin Branch of National Clinical Research Center for Ocular Disease, PR China.
³ Eye Institute and School of Optometry, PR China.
⁴ Tianjin Medical University Eye Hospital, PR China.

Abstract

Mitochondria are important places for the oxidative phosphorylation of glucose and the maintenance of cell oxidation and antioxidant stability. However, mitochondrial dysfunction causes cell dysfunction. Meanwhile, retinal vascular endothelial cell dysfunction may cause vascular inflammation, hemorrhage, angiogenesis, and other manifestations. Our previous studies have shown that Bone morphogenetic protein 4 (BMP4) is an important target for the treatment of retinal neovascularization, but the mechanism remains unclear. Therefore, our study aims to observe the effects of BMP4 on vascular endothelial cells and hopes to provide a new target for diabetic retinopathy. 4-Hydroxynonenal (4HNE), a kind of lipid peroxide, was used to induce the oxidative stress model. Human retinal microvascular endothelial cells (HRMECs) were randomly divided into control, 4HNE, negative control, and siBMP4 groups. Si-BMP4 significantly reduced leukocyte adhesion and 4HNE-induced high ROS level and restored the mitochondrial membrane potential and OCR. This indicates that BMP4 plays an important role in inducing leukocyte adhesion, oxidative stress, and mitochondrial dysfunction. The relationship between BMP4 and retinal vascular endothelial cell dysfunction is preliminarily confirmed by this study. Mitochondrial dysfunction and oxidative stress may be involved in BMP4-mediated retinal vascular endothelial cell dysfunction.

Keywords: BMP4; Mitochondrion; Reactive oxygen species.