2. Academic Validation
  3. SB431542 partially inhibits high glucose-induced EMT by restoring mitochondrial homeostasis in RPE cells

SB431542 partially inhibits high glucose-induced EMT by restoring mitochondrial homeostasis in RPE cells

  • Cell Commun Signal. 2024 Jan 5;22(1):17. doi: 10.1186/s12964-023-01372-1.
Jingjing Cao # 1,  Mingfei Jiao # 1,  Zhenyu Kou # 1,  Feifei Han 1,  Lijie Dong 2
Affiliations

Affiliations

  • 1 Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, 251 Fukang Road, Nankai, Tianjin, 300384, P.R. China.
  • 2 Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, 251 Fukang Road, Nankai, Tianjin, 300384, P.R. China. aitaomubang@126.com.
  • # Contributed equally.
PMID: 38183022 DOI: 10.1186/s12964-023-01372-1
Abstract

Background: The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells participated in the development of retinal fibrosis. SB431542 is a small molecule inhibitor with inhibitory effects on the ALK4, ALK5 and ALK7. Our study aimed to explore the effect of SB431542 on the EMT of RPE cells and to provide new ideas for the treatment of retinal fibrosis.

Methods: We performed fundus fluorescein angiography, optical coherence tomography and hematoxylin-eosin staining in vivo to observe the effect of SB431542 on choroidal neovascularization (CNV)-induced retinopathy. The proliferation, migration, Cytoskeleton, adhesion, Reactive Oxygen Species (ROS), mitochondrial morphology and membrane potential of RPE cells were observed in vitro through fluorescein diacetate staining, Cell Counting Kit-8 experiment, wound healing assay, phalloidin staining, immunofluorescence, MitoSOX, DCFH-DA, MitoTracker and JC-10 staining. Western blot, reverse transcription quantitative and immunofluorescence were used to detect the expression of EMT-related markers, pERK1/2, pGSK3β and β-catenin.

Results: SB431542 significantly alleviated retinopathy in the CNV model. The proliferation, migration and adhesion in RPE cells decreased to a certain extent in SB431542 treatment. SB431542 partially normalized the structure of RPE cells. The expression levels of E-cadherin increased, while the expression levels of laminin and N-Cadherin decreased with SB431542 treatment. SB431542 reduced the production of total ROS, mitochondrial SOX and recovered the mitochondrial membrane potential to a certain degree. In addition, our study showed that SB431542 downregulated the phosphorylation of ERK1/2, GSK3β and the expression of β-catenin.

Conclusion: SB431542 improved EMT in RPE cells by maintaining mitochondrial homeostasis via the ERK1/2 and GSK3β/β-catenin pathways. Video Abstract SB431542 inhibits EMT in RPE cells under high glucose conditions.

Keywords

Epithelial mesenchymal transformation; Mitochondria; Proliferative diabetes retinopathy; RPE; SB431542.

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