Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression
Abstract Adropin is encoded by the energy homeostasis-associated (ENHO) gene and widely present in liver, pancreas, heart, kidney, brain, and vascular tissues. Abnormal adropin is associated with metabolic, inflammatory, immune, and central nervous disorders. Whether adropin is involved in the devel...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-11519-5 |
| _version_ | 1797630198953279488 |
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| author | Linghui Jia Liting Liao Yongshuai Jiang Xiangyu Hu Guotao Lu Weiming Xiao Weijuan Gong Xiaoqin Jia |
| author_facet | Linghui Jia Liting Liao Yongshuai Jiang Xiangyu Hu Guotao Lu Weiming Xiao Weijuan Gong Xiaoqin Jia |
| author_sort | Linghui Jia |
| collection | DOAJ |
| description | Abstract Adropin is encoded by the energy homeostasis-associated (ENHO) gene and widely present in liver, pancreas, heart, kidney, brain, and vascular tissues. Abnormal adropin is associated with metabolic, inflammatory, immune, and central nervous disorders. Whether adropin is involved in the development of colorectal cancer (CRC) is still unclear. Here, decreased adropin expression of tumor-nest cells in advanced-stage CRC was demonstrated. Adropin expressed by carcinoma cells was negatively correlated with macrophage infiltration in the matrix of CRC tissues. However, tumor macrophages enhanced adropin expression and were positively correlated with tumor invasion and metastasis. ENHO gene transfection into colon cancer (MC38) cells inhibited tumor growth in vivo, accompanying the increase of M1 macrophages. Treatment with low-dose adropin (< 100 ng/mL) on macrophages ex vivo directly increased mitochondrial reactive oxygen species for inflammasome activation. Furthermore, ENHO−/− mice had less M1 macrophages in vivo, and ENHO−/− macrophages were inert to be induced into the M1 subset ex vivo. Finally, low-dose adropin promoted glucose utilization, and high-dose adropin enhanced the expression of CPT1α in macrophages. Therefore, variations of adropin level in carcinoma cells or macrophages in tumor tissues are differently involved in CRC progression. Low-dose adropin stimulates the antitumor activity of macrophages, but high-dose adropin facilitates the pro-tumor activity of macrophages. Increasing or decreasing the adropin level can inhibit tumor progression at different CRC stages. |
| first_indexed | 2024-03-11T11:04:48Z |
| format | Article |
| id | doaj.art-db0a16e190a144039283d26295d1d18f |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-11T11:04:48Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-db0a16e190a144039283d26295d1d18f2023-11-12T12:20:19ZengBMCBMC Cancer1471-24072023-10-0123111310.1186/s12885-023-11519-5Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progressionLinghui Jia0Liting Liao1Yongshuai Jiang2Xiangyu Hu3Guotao Lu4Weiming Xiao5Weijuan Gong6Xiaoqin Jia7Department of Basic Medicine, School of Medicine, Yangzhou UniversityDepartment of Basic Medicine, School of Medicine, Yangzhou UniversityDepartment of Basic Medicine, School of Medicine, Yangzhou UniversityDepartment of Basic Medicine, School of Medicine, Yangzhou UniversityDepartment of Gastroenterology, The Affiliated Hospital of Yangzhou UniversityDepartment of Gastroenterology, The Affiliated Hospital of Yangzhou UniversityDepartment of Basic Medicine, School of Medicine, Yangzhou UniversityDepartment of Basic Medicine, School of Medicine, Yangzhou UniversityAbstract Adropin is encoded by the energy homeostasis-associated (ENHO) gene and widely present in liver, pancreas, heart, kidney, brain, and vascular tissues. Abnormal adropin is associated with metabolic, inflammatory, immune, and central nervous disorders. Whether adropin is involved in the development of colorectal cancer (CRC) is still unclear. Here, decreased adropin expression of tumor-nest cells in advanced-stage CRC was demonstrated. Adropin expressed by carcinoma cells was negatively correlated with macrophage infiltration in the matrix of CRC tissues. However, tumor macrophages enhanced adropin expression and were positively correlated with tumor invasion and metastasis. ENHO gene transfection into colon cancer (MC38) cells inhibited tumor growth in vivo, accompanying the increase of M1 macrophages. Treatment with low-dose adropin (< 100 ng/mL) on macrophages ex vivo directly increased mitochondrial reactive oxygen species for inflammasome activation. Furthermore, ENHO−/− mice had less M1 macrophages in vivo, and ENHO−/− macrophages were inert to be induced into the M1 subset ex vivo. Finally, low-dose adropin promoted glucose utilization, and high-dose adropin enhanced the expression of CPT1α in macrophages. Therefore, variations of adropin level in carcinoma cells or macrophages in tumor tissues are differently involved in CRC progression. Low-dose adropin stimulates the antitumor activity of macrophages, but high-dose adropin facilitates the pro-tumor activity of macrophages. Increasing or decreasing the adropin level can inhibit tumor progression at different CRC stages.https://doi.org/10.1186/s12885-023-11519-5AdropinInflammasomemROSMacrophageColorectal cancer |
| spellingShingle | Linghui Jia Liting Liao Yongshuai Jiang Xiangyu Hu Guotao Lu Weiming Xiao Weijuan Gong Xiaoqin Jia Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression BMC Cancer Adropin Inflammasome mROS Macrophage Colorectal cancer |
| title | Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression |
| title_full | Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression |
| title_fullStr | Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression |
| title_full_unstemmed | Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression |
| title_short | Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression |
| title_sort | low dose adropin stimulates inflammasome activation of macrophage via mitochondrial ros involved in colorectal cancer progression |
| topic | Adropin Inflammasome mROS Macrophage Colorectal cancer |
| url | https://doi.org/10.1186/s12885-023-11519-5 |
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