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MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy

OBJECTIVE: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease that involves the remodeling of orbit and periorbital tissues. Thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) may stimulate the activation of autoimmunity in TAO, but the exact...

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Autores principales: Tang, Wei, Lv, Qian, Huang, Xiao, Li, Yuzhen, Zou, JunJie, Zheng, Jiaoyang, Sun, Liangliang, Bao, Yi, Chen, Haiyan, Li, Tuo, Zhang, Bei, Xue, Song, Song, Yan, Zhang, Xingxing, Chen, Xiangfang, Cai, Jiping, Shi, Yongquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898058/
https://www.ncbi.nlm.nih.gov/pubmed/35256853
http://dx.doi.org/10.2147/JIR.S339483
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author Tang, Wei
Lv, Qian
Huang, Xiao
Li, Yuzhen
Zou, JunJie
Zheng, Jiaoyang
Sun, Liangliang
Bao, Yi
Chen, Haiyan
Li, Tuo
Zhang, Bei
Xue, Song
Song, Yan
Zhang, Xingxing
Chen, Xiangfang
Cai, Jiping
Shi, Yongquan
author_facet Tang, Wei
Lv, Qian
Huang, Xiao
Li, Yuzhen
Zou, JunJie
Zheng, Jiaoyang
Sun, Liangliang
Bao, Yi
Chen, Haiyan
Li, Tuo
Zhang, Bei
Xue, Song
Song, Yan
Zhang, Xingxing
Chen, Xiangfang
Cai, Jiping
Shi, Yongquan
author_sort Tang, Wei
collection PubMed
description OBJECTIVE: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease that involves the remodeling of orbit and periorbital tissues. Thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) may stimulate the activation of autoimmunity in TAO, but the exact mechanism is unclear. We investigated whether IGF-1R/TSHR modulation in TAO may involve microRNA regulation. METHODS: We conducted microarray analysis using RNA from the orbital connective tissue samples of 3 healthy and 3 patients with TAO. The involvement of differentially regulated microRNA in IGF-1R/TSHR modulation in TAO was evaluated in orbital fibroblasts (OFs) and female BALB/c mice. RESULTS: Using hierarchical cluster analysis, we identified that miR-143 was downregulated in TAO. The expression levels of miR-143 in OFs were significantly reduced under IL-1B stimulation. However, OF proliferation and inflammatory responses decreased when miR-143 is overexpressed. In contrast, the suppression of miR-143 increased levels of inflammatory markers (IL-6, IL-8, MCP1) and hyaluronan accumulation. Moreover, overexpression of miR-143 significantly lowers levels of IGF-1R and TSHR. A luciferase assay indicated that miR-143 targets the 3′-UTR of IGF-1R. Increases in the expression of IGF-1R increased the expression of the inflammasome marker NLRP3 and apoptotic marker cleaved caspase-1; however, miR-143 overexpression decreased levels of IGF-1R, TSHR, NLRP3, cleaved caspase 1, IL-1B, and IL-18. In a mouse model of TAO, overexpression of miR-143 significantly reduced levels of IGF-1R and attenuated the adipogenesis associated with TAO. CONCLUSION: We found that miR-143 directly targets IGF-1R to alleviate the inflammatory response in TAO by indirectly decreasing levels of TSHR and inactivating NLRP3.
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spelling pubmed-88980582022-03-06 MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy Tang, Wei Lv, Qian Huang, Xiao Li, Yuzhen Zou, JunJie Zheng, Jiaoyang Sun, Liangliang Bao, Yi Chen, Haiyan Li, Tuo Zhang, Bei Xue, Song Song, Yan Zhang, Xingxing Chen, Xiangfang Cai, Jiping Shi, Yongquan J Inflamm Res Original Research OBJECTIVE: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease that involves the remodeling of orbit and periorbital tissues. Thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) may stimulate the activation of autoimmunity in TAO, but the exact mechanism is unclear. We investigated whether IGF-1R/TSHR modulation in TAO may involve microRNA regulation. METHODS: We conducted microarray analysis using RNA from the orbital connective tissue samples of 3 healthy and 3 patients with TAO. The involvement of differentially regulated microRNA in IGF-1R/TSHR modulation in TAO was evaluated in orbital fibroblasts (OFs) and female BALB/c mice. RESULTS: Using hierarchical cluster analysis, we identified that miR-143 was downregulated in TAO. The expression levels of miR-143 in OFs were significantly reduced under IL-1B stimulation. However, OF proliferation and inflammatory responses decreased when miR-143 is overexpressed. In contrast, the suppression of miR-143 increased levels of inflammatory markers (IL-6, IL-8, MCP1) and hyaluronan accumulation. Moreover, overexpression of miR-143 significantly lowers levels of IGF-1R and TSHR. A luciferase assay indicated that miR-143 targets the 3′-UTR of IGF-1R. Increases in the expression of IGF-1R increased the expression of the inflammasome marker NLRP3 and apoptotic marker cleaved caspase-1; however, miR-143 overexpression decreased levels of IGF-1R, TSHR, NLRP3, cleaved caspase 1, IL-1B, and IL-18. In a mouse model of TAO, overexpression of miR-143 significantly reduced levels of IGF-1R and attenuated the adipogenesis associated with TAO. CONCLUSION: We found that miR-143 directly targets IGF-1R to alleviate the inflammatory response in TAO by indirectly decreasing levels of TSHR and inactivating NLRP3. Dove 2022-03-01 /pmc/articles/PMC8898058/ /pubmed/35256853 http://dx.doi.org/10.2147/JIR.S339483 Text en © 2022 Tang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Tang, Wei
Lv, Qian
Huang, Xiao
Li, Yuzhen
Zou, JunJie
Zheng, Jiaoyang
Sun, Liangliang
Bao, Yi
Chen, Haiyan
Li, Tuo
Zhang, Bei
Xue, Song
Song, Yan
Zhang, Xingxing
Chen, Xiangfang
Cai, Jiping
Shi, Yongquan
MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy
title MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy
title_full MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy
title_fullStr MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy
title_full_unstemmed MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy
title_short MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy
title_sort mir-143 targets igf-1r to suppress autoimmunity in thyroid-associated ophthalmopathy
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898058/
https://www.ncbi.nlm.nih.gov/pubmed/35256853
http://dx.doi.org/10.2147/JIR.S339483
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