GLIS3 mediated by the Rap1/PI3K/AKT signal pathway facilitates real-ambient PM2.5 exposure disturbed thyroid hormone homeostasis regulation
Exposure to fine particulate matter (PM2.5) could damage multiple organs and systems. Recent epidemiological studies have shown that PM2.5 can disrupt dynamic balance of thyroid hormone (TH). However, the underlying mechanism by which PM2.5 interferes with TH remains unclear. This study evaluated th...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322000884 |
| _version_ | 1818297017640681472 |
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| author | Siying Tang Daochuan Li Hao Ding Menghui Jiang Yanjie Zhao Dianke Yu Rong Zhang Wen Chen Rui Chen Yuxin Zheng Jinmei Piao |
| author_facet | Siying Tang Daochuan Li Hao Ding Menghui Jiang Yanjie Zhao Dianke Yu Rong Zhang Wen Chen Rui Chen Yuxin Zheng Jinmei Piao |
| author_sort | Siying Tang |
| collection | DOAJ |
| description | Exposure to fine particulate matter (PM2.5) could damage multiple organs and systems. Recent epidemiological studies have shown that PM2.5 can disrupt dynamic balance of thyroid hormone (TH). However, the underlying mechanism by which PM2.5 interferes with TH remains unclear. This study evaluated the role of Gli-similar3 (GLIS3) in the effect of PM2.5 on TH synthesis in mice using a real-ambient exposure system, in Shijiazhuang City, Hebei Province. The PM2.5exposure group (PM) and filtered air group (FA) were placed in the exposure device for four and eight weeks. The results showed that the PM2.5 exposure altered the structure of the thyroid gland. Moreover, after PM2.5 exposure for eight weeks, the exposure level of free thyroxine (FT4) increased and the expression level of thyroid stimulating hormone (TSH) decreased in serum of mice. In addition, PM2.5 exposure significantly increased the expression of proteins related to thyroid hormone synthesis, such as sodium iodide transporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG). Next, we found that GLIS3 and thyroid transcription factor Paired box 8 (PAX8) also increased after PM2.5 exposure. In order to further explore the potential molecular mechanism, we carried out transcriptome sequencing. KEGG analysis of the top 10 pathways revealed that the Ras-associated protein 1 (Rap1) signaling pathway could activate transcription factors and is related to thyroid cell survival. Additionally, PM2.5 exposure significantly increased the protein levels of Rap1 and its active form (Rap1 +GTP). We speculate that the active state of Rap1 is believed to be involved in activating the expression of transcription factor GLIS3. In conclusion, PM2.5 exposure induces histological changes in the thyroid gland and thyroid dysfunction in mice. The exposure activates GLIS3 through the Rap1/PI3K/AKT pathway to promote the expression of proteins related to thyroid hormone synthesis, leading to increased dysregulating TH homeostasis. |
| first_indexed | 2024-12-13T04:12:45Z |
| format | Article |
| id | doaj.art-759e7643eaef47d78cf06d0f4d080abc |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-13T04:12:45Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-759e7643eaef47d78cf06d0f4d080abc2022-12-21T23:59:57ZengElsevierEcotoxicology and Environmental Safety0147-65132022-03-01232113248GLIS3 mediated by the Rap1/PI3K/AKT signal pathway facilitates real-ambient PM2.5 exposure disturbed thyroid hormone homeostasis regulationSiying Tang0Daochuan Li1Hao Ding2Menghui Jiang3Yanjie Zhao4Dianke Yu5Rong Zhang6Wen Chen7Rui Chen8Yuxin Zheng9Jinmei Piao10School of Public Health, Qingdao University, Qingdao 266021, Shandong Province, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, ChinaSchool of Public Health, Qingdao University, Qingdao 266021, Shandong Province, China; The Second People's Hospital of Qidong, Nantong 226200, Jiangsu Province, ChinaSchool of Public Health, Qingdao University, Qingdao 266021, Shandong Province, ChinaSchool of Public Health, Qingdao University, Qingdao 266021, Shandong Province, ChinaSchool of Public Health, Qingdao University, Qingdao 266021, Shandong Province, ChinaDepartment of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang 050017, Hebei Province, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, ChinaSchool of Public Health, Capital Medical University, Beijing 100000, ChinaSchool of Public Health, Qingdao University, Qingdao 266021, Shandong Province, ChinaSchool of Public Health, Qingdao University, Qingdao 266021, Shandong Province, China; Corresponding author.Exposure to fine particulate matter (PM2.5) could damage multiple organs and systems. Recent epidemiological studies have shown that PM2.5 can disrupt dynamic balance of thyroid hormone (TH). However, the underlying mechanism by which PM2.5 interferes with TH remains unclear. This study evaluated the role of Gli-similar3 (GLIS3) in the effect of PM2.5 on TH synthesis in mice using a real-ambient exposure system, in Shijiazhuang City, Hebei Province. The PM2.5exposure group (PM) and filtered air group (FA) were placed in the exposure device for four and eight weeks. The results showed that the PM2.5 exposure altered the structure of the thyroid gland. Moreover, after PM2.5 exposure for eight weeks, the exposure level of free thyroxine (FT4) increased and the expression level of thyroid stimulating hormone (TSH) decreased in serum of mice. In addition, PM2.5 exposure significantly increased the expression of proteins related to thyroid hormone synthesis, such as sodium iodide transporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG). Next, we found that GLIS3 and thyroid transcription factor Paired box 8 (PAX8) also increased after PM2.5 exposure. In order to further explore the potential molecular mechanism, we carried out transcriptome sequencing. KEGG analysis of the top 10 pathways revealed that the Ras-associated protein 1 (Rap1) signaling pathway could activate transcription factors and is related to thyroid cell survival. Additionally, PM2.5 exposure significantly increased the protein levels of Rap1 and its active form (Rap1 +GTP). We speculate that the active state of Rap1 is believed to be involved in activating the expression of transcription factor GLIS3. In conclusion, PM2.5 exposure induces histological changes in the thyroid gland and thyroid dysfunction in mice. The exposure activates GLIS3 through the Rap1/PI3K/AKT pathway to promote the expression of proteins related to thyroid hormone synthesis, leading to increased dysregulating TH homeostasis.http://www.sciencedirect.com/science/article/pii/S0147651322000884PM2.5Thyroid glandGLIS3Real-ambient PM exposure system |
| spellingShingle | Siying Tang Daochuan Li Hao Ding Menghui Jiang Yanjie Zhao Dianke Yu Rong Zhang Wen Chen Rui Chen Yuxin Zheng Jinmei Piao GLIS3 mediated by the Rap1/PI3K/AKT signal pathway facilitates real-ambient PM2.5 exposure disturbed thyroid hormone homeostasis regulation Ecotoxicology and Environmental Safety PM2.5 Thyroid gland GLIS3 Real-ambient PM exposure system |
| title | GLIS3 mediated by the Rap1/PI3K/AKT signal pathway facilitates real-ambient PM2.5 exposure disturbed thyroid hormone homeostasis regulation |
| title_full | GLIS3 mediated by the Rap1/PI3K/AKT signal pathway facilitates real-ambient PM2.5 exposure disturbed thyroid hormone homeostasis regulation |
| title_fullStr | GLIS3 mediated by the Rap1/PI3K/AKT signal pathway facilitates real-ambient PM2.5 exposure disturbed thyroid hormone homeostasis regulation |
| title_full_unstemmed | GLIS3 mediated by the Rap1/PI3K/AKT signal pathway facilitates real-ambient PM2.5 exposure disturbed thyroid hormone homeostasis regulation |
| title_short | GLIS3 mediated by the Rap1/PI3K/AKT signal pathway facilitates real-ambient PM2.5 exposure disturbed thyroid hormone homeostasis regulation |
| title_sort | glis3 mediated by the rap1 pi3k akt signal pathway facilitates real ambient pm2 5 exposure disturbed thyroid hormone homeostasis regulation |
| topic | PM2.5 Thyroid gland GLIS3 Real-ambient PM exposure system |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322000884 |
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