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Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
Published on: October 6, 2023
Comparative effects of transforming growth factor beta isoforms on redox metabolism in thyroid cells
Romina Oglio1, Lisa Thomasz2, Leonardo Salvarredi1
1Nuclear Biochemistry Division, Argentine National Atomic Energy Commission, Buenos Aires 1429, Argentina.
Introduction:
Transforming growth factor beta (TGF-β) regulates thyroid function and growth. However, tumoral thyroid cells became resistant to this factor as they undifferentiated. Little is known about the effects of TGF-β isoforms. We compared the role of redox metabolism in the response to TGF-β isoforms between non tumoral and tumoral thyroid cells.
Methodology And Results:
Differentiated rat thyroid cells (FRTL-5) and human thyroid follicular carcinoma cells (WRO) were treated with the three isoforms of TGF-β. TGF-β isoforms stopped cell cycle at different steps; G1 for FRTL-5 and G2/M for WRO. The three isoforms decreased cell viability and increased ROS accumulation in both cell lines. These effects were more pronounced in FRTL-5 than in WRO, and the isoform β1 was more potent in ROS production than the other two. TGF-β isoforms decreased total glutathione, catalase expression and it activity in both cell lines. Only in FRTL-5 the lipid peroxidation was demonstrated. Moreover, TGF-β1 decreased glutathione peroxidase and mitochondrial superoxide dismutase mRNA expression and increased mitochondrial ROS in FRTL-5, but no in WRO. Pretreatment with selenium increased glutathione peroxidase activity and decreased ROS production in WRO treated with TGF-β isoforms. Furthermore, selenium partially reversed the effect of TGF-β isoforms on cell viability only in WRO cells. The knockdown of endogenous NOX4 significantly reduced the TGF-β1 effect on cell viability in WRO but no in FRTL-5.
Conclusion:
TGF-β disrupted the redox balance and increased ROS accumulation in both cell lines. FRTL-5 cells showed reduced antioxidant capacity and had a greater sensitivity to TGF-β isoforms, while WRO cells were more resistant. This observation provides new insights into the potential role of TGF-β in the redox regulation of thyroid cells.
Insights
Transforming growth factor beta (TGF-β) disrupts redox balance in thyroid cells, increasing reactive oxygen species (ROS). Differentiated cells are more sensitive to TGF-β than tumoral cells, highlighting redox metabolism
Area of Science:
- Endocrinology
- Cell Biology
- Biochemistry
Background:
- Transforming growth factor beta (TGF-β) is crucial for thyroid function and growth.
- Tumoral thyroid cells often develop resistance to TGF-β.
- The specific roles of different TGF-β isoforms in thyroid cell redox metabolism are not well understood.
Purpose of the Study:
- To compare the effects of TGF-β isoforms on redox metabolism in non-tumoral (FRTL-5) and tumoral (WRO) thyroid cells.
- To investigate the differential responses of these cell types to TGF-β-induced oxidative stress.
Main Methods:
- Treatment of FRTL-5 and WRO cells with TGF-β isoforms.
- Assessment of cell cycle progression, viability, and reactive oxygen species (ROS) accumulation.
- Measurement of antioxidant markers including glutathione and catalase.
- Analysis of specific enzyme expression (glutathione peroxidase, superoxide dismutase) and lipid peroxidation.
- Intervention with selenium and NOX4 knockdown.
Main Results:
- TGF-β isoforms induced cell cycle arrest (G1 in FRTL-5, G2/M in WRO) and decreased viability in both cell lines.
- ROS accumulation and disruption of redox balance were observed in both cell types, with greater impact on FRTL-5 cells.
- TGF-β isoform β1 showed higher potency in ROS production.
- Antioxidant capacity was reduced in FRTL-5 cells, making them more sensitive.
- Selenium pretreatment mitigated ROS and partially restored viability in WRO cells.
- NOX4 knockdown affected TGF-β1's impact on WRO cell viability.
Conclusions:
- TGF-β isoforms significantly disrupt the redox balance in thyroid cells, leading to increased ROS.
- Differentiated thyroid cells (FRTL-5) exhibit reduced antioxidant capacity and higher sensitivity to TGF-β compared to tumoral cells (WRO).
- These findings offer new insights into TGF-β's role in thyroid cell redox regulation and potential therapeutic targets.
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