Next Article in Journal
Identification of an Epigenetically Marked Locus within the Sex Determination Region of Channel Catfish
Previous Article in Journal
Identification and Transcriptome Analysis of Genes Related to Membrane Lipid Regulation in Sweet Sorghum under Salt Stress
Previous Article in Special Issue
Chronic Intermittent Hypoxia Exposure Alternative to Exercise Alleviates High-Fat-Diet-Induced Obesity and Fatty Liver
Article

Hypoxia Differently Affects TGF-β2-Induced Epithelial Mesenchymal Transitions in the 2D and 3D Culture of the Human Retinal Pigment Epithelium Cells

1
Department of Ophthalmology, School of Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan
2
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan
3
Department of Cellular Physiology and Signal Transduction, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Ludmila D. Lukyanova and Elena Rybnikova
Int. J. Mol. Sci. 2022, 23(10), 5473; https://doi.org/10.3390/ijms23105473 (registering DOI)
Received: 1 April 2022 / Revised: 27 April 2022 / Accepted: 11 May 2022 / Published: 13 May 2022
(This article belongs to the Special Issue Molecular Mechanisms of Adaptation to Hypoxia)
The hypoxia associated with the transforming growth factor-β2 (TGF-β2)-induced epithelial mesenchymal transition (EMT) of human retinal pigment epithelium (HRPE) cells is well recognized as the essential underlying mechanism responsible for the development of proliferative retinal diseases. In vitro, three-dimensional (3D) models associated with spontaneous O2 gradients can be used to recapitulate the pathological levels of hypoxia to study the effect of hypoxia on the TGF-β2-induced EMT of HRPE cells in detail, we used two-dimensional-(2D) and 3D-cultured HRPE cells. TGF-β2 and hypoxia significantly and synergistically increased the barrier function of the 2D HRPE monolayers, as evidenced by TEER measurements, the downsizing and stiffening of the 3D HRPE spheroids and the mRNA expression of most of the ECM proteins. A real-time metabolic analysis indicated that TGF-β2 caused a decrease in the maximal capacity of mitochondrial oxidative phosphorylation in the 2D HRPE cells, whereas, in the case of 3D HRPE spheroids, TGF-β2 increased proton leakage. The findings reported herein indicate that the TGF-β2-induced EMT of both the 2D and 3D cultured HRPE cells were greatly modified by hypoxia, but during these EMT processes, the metabolic plasticity was different between 2D and 3D HRPE cells, suggesting that the mechanisms responsible for the EMT of the HRPE cells may be variable during their spatial spreading. View Full-Text
Keywords: TGF-β2; human retinal pigment epithelium; 3D culture TGF-β2; human retinal pigment epithelium; 3D culture
Show Figures

Figure 1

MDPI and ACS Style

Suzuki, S.; Sato, T.; Watanabe, M.; Higashide, M.; Tsugeno, Y.; Umetsu, A.; Furuhashi, M.; Ida, Y.; Hikage, F.; Ohguro, H. Hypoxia Differently Affects TGF-β2-Induced Epithelial Mesenchymal Transitions in the 2D and 3D Culture of the Human Retinal Pigment Epithelium Cells. Int. J. Mol. Sci. 2022, 23, 5473. https://doi.org/10.3390/ijms23105473

AMA Style

Suzuki S, Sato T, Watanabe M, Higashide M, Tsugeno Y, Umetsu A, Furuhashi M, Ida Y, Hikage F, Ohguro H. Hypoxia Differently Affects TGF-β2-Induced Epithelial Mesenchymal Transitions in the 2D and 3D Culture of the Human Retinal Pigment Epithelium Cells. International Journal of Molecular Sciences. 2022; 23(10):5473. https://doi.org/10.3390/ijms23105473

Chicago/Turabian Style

Suzuki, Soma, Tatsuya Sato, Megumi Watanabe, Megumi Higashide, Yuri Tsugeno, Araya Umetsu, Masato Furuhashi, Yosuke Ida, Fumihito Hikage, and Hiroshi Ohguro. 2022. "Hypoxia Differently Affects TGF-β2-Induced Epithelial Mesenchymal Transitions in the 2D and 3D Culture of the Human Retinal Pigment Epithelium Cells" International Journal of Molecular Sciences 23, no. 10: 5473. https://doi.org/10.3390/ijms23105473

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop