Next Article in Journal
Liver Fibrosis Leading to Cirrhosis: Basic Mechanisms and Clinical Perspectives
Next Article in Special Issue
Advancing Hydrogel-Based 3D Cell Culture Systems: Histological Image Analysis and AI-Driven Filament Characterization
Previous Article in Journal
Treatment of Refractory Mucosal Leishmaniasis Is Associated with Parasite Overexpression of HSP70 and ATPase and Reduced Host Hydrogen Peroxide Production (Brief Report)
Previous Article in Special Issue
Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Reversing Hepatic Fibrosis in 3D Liver Spheroids
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biomedicines
Volume 12
Issue 10
10.3390/biomedicines12102228
biomedicines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Unexpected and Synergistical Effects of All-Trans Retinoic Acid and TGF-β2 on Biological Aspects of 2D and 3D Cultured ARPE19 Cells

by
Megumi Higashide
1,
Megumi Watanabe
1,
Tatsuya Sato
2,3,
Toshifumi Ogawa
2,3,
Araya Umetsu
1,
Soma Suzuki
1,
Masato Furuhashi
2,
Hiroshi Ohguro
1 and
Nami Nishikiori
1,*
1
Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan
2
Departments of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan
3
Departments of Cellular Physiology and Signal Transduction, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan
*
Author to whom correspondence should be addressed.
Biomedicines 2024, 12(10), 2228; https://doi.org/10.3390/biomedicines12102228
Submission received: 2 September 2024 / Revised: 24 September 2024 / Accepted: 26 September 2024 / Published: 30 September 2024
(This article belongs to the Special Issue 3D Cell Culture Systems for Biomedical Research)
Browse Figures
Review Reports Versions Notes

Abstract

Objectives: To study the effects of all-trans retinoic acid (ATRA) on TGF-β2-induced effects of human retinal pigment epithelium cells under normoxia and hypoxia conditions. Methods: Two-dimensionally (2D) and three-dimensionally (3D) cultured ARPE19 cells were subjected to cellular functional analyses by transepithelial electrical resistance (TEER) and an extracellular flux assay (2D), measurement of levels of reactive oxygen species (ROS), gene expression analyses of COL1, αSMA, Zo-1, HIF1α, and PGC1α (2D), and physical property analyses (3D). Results: Under a normoxia condition, treatment with 100 nM ATRA substantially decreased barrier function regardless of the presence of 5 ng/mL TGF-β2 in 2D ARPE19 monolayer cells. Under a hypoxia condition, treatment with ATRA conversely increased barrier function, but the effect was masked by a marked increase in effects induced by TGF-β2. Although ATRA alone did not affect cellular metabolism and ROS levels in 2D ARPE cells, treatment with ATRA under a hypoxia condition did not affect ROS levels but shifted cellular metabolism from mitochondrial respiration to glycolysis. The changes of cellular metabolism and ROS levels were more pronounced with treatment of both ATRA and TGF-β2 independently of oxygen conditions. Changes in mRNA expressions of some of the above genes suggested the involvement of synergistical regulation of cellular functions by TGF-β2 and hypoxia. In 3D ARPE spheroids, the size was decreased and the stiffness was increased by either treatment with TGF-β2 or ATRA, but these changes were unexpectedly modulated by both ATRA and TGF-β2 treatment regardless of oxygen conditions. Conclusions: The findings reported herein indicate that TGF-β2 and hypoxia synergistically and differentially induce effects in 2D and 3D cultured ARPE19 cells and that their cellular properties are significantly altered by the presence of ATRA.
Keywords: TGF-β2; human retinal pigment epithelium; 3D culture; ATRA; hypoxia TGF-β2; human retinal pigment epithelium; 3D culture; ATRA; hypoxia

Share and Cite

MDPI and ACS Style

Higashide, M.; Watanabe, M.; Sato, T.; Ogawa, T.; Umetsu, A.; Suzuki, S.; Furuhashi, M.; Ohguro, H.; Nishikiori, N. Unexpected and Synergistical Effects of All-Trans Retinoic Acid and TGF-β2 on Biological Aspects of 2D and 3D Cultured ARPE19 Cells. Biomedicines 2024, 12, 2228. https://doi.org/10.3390/biomedicines12102228

AMA Style

Higashide M, Watanabe M, Sato T, Ogawa T, Umetsu A, Suzuki S, Furuhashi M, Ohguro H, Nishikiori N. Unexpected and Synergistical Effects of All-Trans Retinoic Acid and TGF-β2 on Biological Aspects of 2D and 3D Cultured ARPE19 Cells. Biomedicines. 2024; 12(10):2228. https://doi.org/10.3390/biomedicines12102228

Chicago/Turabian Style

Higashide, Megumi, Megumi Watanabe, Tatsuya Sato, Toshifumi Ogawa, Araya Umetsu, Soma Suzuki, Masato Furuhashi, Hiroshi Ohguro, and Nami Nishikiori. 2024. "Unexpected and Synergistical Effects of All-Trans Retinoic Acid and TGF-β2 on Biological Aspects of 2D and 3D Cultured ARPE19 Cells" Biomedicines 12, no. 10: 2228. https://doi.org/10.3390/biomedicines12102228

APA Style

Higashide, M., Watanabe, M., Sato, T., Ogawa, T., Umetsu, A., Suzuki, S., Furuhashi, M., Ohguro, H., & Nishikiori, N. (2024). Unexpected and Synergistical Effects of All-Trans Retinoic Acid and TGF-β2 on Biological Aspects of 2D and 3D Cultured ARPE19 Cells. Biomedicines, 12(10), 2228. https://doi.org/10.3390/biomedicines12102228

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop