Investigation of the Molecular Mechanisms by Which Endothelin-3 Stimulates Preadipocyte Growth
Endothelins induce many biological responses, and they are composed of three peptides: ET-1, ET-2, and ET-3. Reports have indicated that ET-1 regulates cell proliferation, adipogenesis, and other cell responses and that ET-3 stimulates the growth of gastrointestinal epithelial cells and melanocytes....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.661828/full |
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| author | An-Ci Siao Li-Jane Shih Li-Jane Shih Yen-Yue Lin Yen-Yue Lin Yen-Yue Lin Yi-Wei Tsuei Yow-Chii Kuo Hui-Chen Ku Chih-Ping Chuu Po-Jen Hsiao Po-Jen Hsiao Po-Jen Hsiao Po-Jen Hsiao Yung-Hsi Kao |
| author_facet | An-Ci Siao Li-Jane Shih Li-Jane Shih Yen-Yue Lin Yen-Yue Lin Yen-Yue Lin Yi-Wei Tsuei Yow-Chii Kuo Hui-Chen Ku Chih-Ping Chuu Po-Jen Hsiao Po-Jen Hsiao Po-Jen Hsiao Po-Jen Hsiao Yung-Hsi Kao |
| author_sort | An-Ci Siao |
| collection | DOAJ |
| description | Endothelins induce many biological responses, and they are composed of three peptides: ET-1, ET-2, and ET-3. Reports have indicated that ET-1 regulates cell proliferation, adipogenesis, and other cell responses and that ET-3 stimulates the growth of gastrointestinal epithelial cells and melanocytes. However, the signalling pathways of ET3 that mediate the growth of fat cells are still unclear. Using 3T3-L1 white preadipocytes, we found that ET-3 induced increases in both cell number and BrdU incorporation. Pretreatment with an ETAR antagonist (but not an ETBR antagonist) blocked the ET-3-induced increases in both cell number and BrdU incorporation. Additionally, BQ610 suppressed the ET-3-induced increases in phosphorylation of AMPK, c-JUN, and STAT3 proteins, and pretreatment with specific inhibitors of AMPK, JNK/c-JUN, or JAK/STAT3 prevented the ET-3-induced increases in phosphorylation of AMPK, c-JUN, and STAT3, respectively. Neither p38 MAPK inhibitor nor PKC inhibitor altered the effects of ET-3 on cell growth. These data suggest that ET-3 stimulates preadipocyte growth through the ETAR, AMPK, JNK/c-JUN, and STAT3 pathways. Moreover, ET-3 did not alter HIB1B brown preadipocyte and D12 beige preadipocyte growth, suggesting a preadipocyte type-dependent effect. The results of this study may help explain how endothelin mediates fat cell activity and fat cell-associated diseases. |
| first_indexed | 2024-12-14T21:47:54Z |
| format | Article |
| id | doaj.art-73d929ad33dc43e582c04b2f262f9504 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-14T21:47:54Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-73d929ad33dc43e582c04b2f262f95042022-12-21T22:46:18ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-05-011210.3389/fendo.2021.661828661828Investigation of the Molecular Mechanisms by Which Endothelin-3 Stimulates Preadipocyte GrowthAn-Ci Siao0Li-Jane Shih1Li-Jane Shih2Yen-Yue Lin3Yen-Yue Lin4Yen-Yue Lin5Yi-Wei Tsuei6Yow-Chii Kuo7Hui-Chen Ku8Chih-Ping Chuu9Po-Jen Hsiao10Po-Jen Hsiao11Po-Jen Hsiao12Po-Jen Hsiao13Yung-Hsi Kao14Department of Life Sciences, National Central University, Taoyuan, TaiwanMedical Laboratory, Taoyuan Armed Forces General Hospital, Taoyuan, TaiwanGraduate Institute of Medical Science, National Defense Medical Center, Taipei, TaiwanDepartment of Life Sciences, National Central University, Taoyuan, TaiwanDepartment of Emergency Medicine, Taoyuan Armed Forces General Hospital, Taoyuan City, TaiwanDepartment of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDepartment of Emergency Medicine, Taoyuan Armed Forces General Hospital, Taoyuan City, TaiwanDepartment of Gastroenterology, Landseed Hospital, Taoyuan, TaiwanDepartment of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanInstitute of Cellular and System Medicine, National Health Research Institutes, Zhunan, TaiwanDepartment of Life Sciences, National Central University, Taoyuan, TaiwanInstitute of Cellular and System Medicine, National Health Research Institutes, Zhunan, TaiwanDivision of Nephrology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan City, Taiwan0Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDepartment of Life Sciences, National Central University, Taoyuan, TaiwanEndothelins induce many biological responses, and they are composed of three peptides: ET-1, ET-2, and ET-3. Reports have indicated that ET-1 regulates cell proliferation, adipogenesis, and other cell responses and that ET-3 stimulates the growth of gastrointestinal epithelial cells and melanocytes. However, the signalling pathways of ET3 that mediate the growth of fat cells are still unclear. Using 3T3-L1 white preadipocytes, we found that ET-3 induced increases in both cell number and BrdU incorporation. Pretreatment with an ETAR antagonist (but not an ETBR antagonist) blocked the ET-3-induced increases in both cell number and BrdU incorporation. Additionally, BQ610 suppressed the ET-3-induced increases in phosphorylation of AMPK, c-JUN, and STAT3 proteins, and pretreatment with specific inhibitors of AMPK, JNK/c-JUN, or JAK/STAT3 prevented the ET-3-induced increases in phosphorylation of AMPK, c-JUN, and STAT3, respectively. Neither p38 MAPK inhibitor nor PKC inhibitor altered the effects of ET-3 on cell growth. These data suggest that ET-3 stimulates preadipocyte growth through the ETAR, AMPK, JNK/c-JUN, and STAT3 pathways. Moreover, ET-3 did not alter HIB1B brown preadipocyte and D12 beige preadipocyte growth, suggesting a preadipocyte type-dependent effect. The results of this study may help explain how endothelin mediates fat cell activity and fat cell-associated diseases.https://www.frontiersin.org/articles/10.3389/fendo.2021.661828/fullendothelin-3preadipocyteAMP-activated protein kinasesignal transducer and activator of transcriptionc-Jun |
| spellingShingle | An-Ci Siao Li-Jane Shih Li-Jane Shih Yen-Yue Lin Yen-Yue Lin Yen-Yue Lin Yi-Wei Tsuei Yow-Chii Kuo Hui-Chen Ku Chih-Ping Chuu Po-Jen Hsiao Po-Jen Hsiao Po-Jen Hsiao Po-Jen Hsiao Yung-Hsi Kao Investigation of the Molecular Mechanisms by Which Endothelin-3 Stimulates Preadipocyte Growth Frontiers in Endocrinology endothelin-3 preadipocyte AMP-activated protein kinase signal transducer and activator of transcription c-Jun |
| title | Investigation of the Molecular Mechanisms by Which Endothelin-3 Stimulates Preadipocyte Growth |
| title_full | Investigation of the Molecular Mechanisms by Which Endothelin-3 Stimulates Preadipocyte Growth |
| title_fullStr | Investigation of the Molecular Mechanisms by Which Endothelin-3 Stimulates Preadipocyte Growth |
| title_full_unstemmed | Investigation of the Molecular Mechanisms by Which Endothelin-3 Stimulates Preadipocyte Growth |
| title_short | Investigation of the Molecular Mechanisms by Which Endothelin-3 Stimulates Preadipocyte Growth |
| title_sort | investigation of the molecular mechanisms by which endothelin 3 stimulates preadipocyte growth |
| topic | endothelin-3 preadipocyte AMP-activated protein kinase signal transducer and activator of transcription c-Jun |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.661828/full |
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