AIM2 promotes excitatory glutamate receptor expression by inhibiting STING and contributes to bone cancer pain in male mice
Abstract Bone cancer pain (BCP) is a common clinical problem in cancer patients. The plasticity of excitatory neurons within the spinal dorsal horn plays a significant role in the development of BCP. This study explored the roles of absent in melanoma 2 (AIM2) and stimulator of interferon gene (STIN...
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Nature Portfolio
2024-12-01
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| Online Access: | https://doi.org/10.1038/s41598-024-83027-w |
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| author | Linhan Wang Xueqin Xu Shanchun Su Biyun Li Kunyu Zhang Xiuqin Yu Yangqiao Xiao Shuangshuang Lu Zihao Lu Yanqiong Wu Changbin Ke |
| author_facet | Linhan Wang Xueqin Xu Shanchun Su Biyun Li Kunyu Zhang Xiuqin Yu Yangqiao Xiao Shuangshuang Lu Zihao Lu Yanqiong Wu Changbin Ke |
| author_sort | Linhan Wang |
| collection | DOAJ |
| description | Abstract Bone cancer pain (BCP) is a common clinical problem in cancer patients. The plasticity of excitatory neurons within the spinal dorsal horn plays a significant role in the development of BCP. This study explored the roles of absent in melanoma 2 (AIM2) and stimulator of interferon gene (STING) in BCP using male C57BL/6J mice. Cancers cells were cultured and implanted into the tibia to induce pain-like behavior. AIM2-RNAi lentivirus was injected into spinal dorsal horn or STING agonist was injected intraperitoneally. The protein expressions and localization were evaluated by qRT-PCR and WB or IF, respectively. The mechanical pain threshold was measured using the von Frey test. Immunofluorescence showed that AIM2 and STING were co-localized in spinal cord neurons, and AIM2 was expressed in the presynaptic membrane. qRT-PCR and western blotting showed that AIM2 expression was increased, and STING expression was decreased in cancer implanted mice. Inhibition of AIM2 enhanced the expression of STING and reduced the expression of GluN1, and attenuated mechanical allodynia. After injecting of STING agonist, the mechanical pain threshold was increased and the expression of GluN1 was decreased. These results emphasizes the involvement of AIM2 in BCP development by downregulating STING expression and increasing GluN1 expression. |
| format | Article |
| id | doaj-art-79b081a0fb554f549fe4d2e77ff1c47f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-79b081a0fb554f549fe4d2e77ff1c47f2025-01-05T12:24:52ZengNature PortfolioScientific Reports2045-23222024-12-0114111510.1038/s41598-024-83027-wAIM2 promotes excitatory glutamate receptor expression by inhibiting STING and contributes to bone cancer pain in male miceLinhan Wang0Xueqin Xu1Shanchun Su2Biyun Li3Kunyu Zhang4Xiuqin Yu5Yangqiao Xiao6Shuangshuang Lu7Zihao Lu8Yanqiong Wu9Changbin Ke10Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineInstitute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineInstitute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineInstitute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineInstitute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineInstitute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineInstitute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineInstitute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineInstitute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineInstitute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineInstitute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of MedicineAbstract Bone cancer pain (BCP) is a common clinical problem in cancer patients. The plasticity of excitatory neurons within the spinal dorsal horn plays a significant role in the development of BCP. This study explored the roles of absent in melanoma 2 (AIM2) and stimulator of interferon gene (STING) in BCP using male C57BL/6J mice. Cancers cells were cultured and implanted into the tibia to induce pain-like behavior. AIM2-RNAi lentivirus was injected into spinal dorsal horn or STING agonist was injected intraperitoneally. The protein expressions and localization were evaluated by qRT-PCR and WB or IF, respectively. The mechanical pain threshold was measured using the von Frey test. Immunofluorescence showed that AIM2 and STING were co-localized in spinal cord neurons, and AIM2 was expressed in the presynaptic membrane. qRT-PCR and western blotting showed that AIM2 expression was increased, and STING expression was decreased in cancer implanted mice. Inhibition of AIM2 enhanced the expression of STING and reduced the expression of GluN1, and attenuated mechanical allodynia. After injecting of STING agonist, the mechanical pain threshold was increased and the expression of GluN1 was decreased. These results emphasizes the involvement of AIM2 in BCP development by downregulating STING expression and increasing GluN1 expression.https://doi.org/10.1038/s41598-024-83027-wAIM2STINGGluN1Spinal cordBone cancer pain |
| spellingShingle | Linhan Wang Xueqin Xu Shanchun Su Biyun Li Kunyu Zhang Xiuqin Yu Yangqiao Xiao Shuangshuang Lu Zihao Lu Yanqiong Wu Changbin Ke AIM2 promotes excitatory glutamate receptor expression by inhibiting STING and contributes to bone cancer pain in male mice Scientific Reports AIM2 STING GluN1 Spinal cord Bone cancer pain |
| title | AIM2 promotes excitatory glutamate receptor expression by inhibiting STING and contributes to bone cancer pain in male mice |
| title_full | AIM2 promotes excitatory glutamate receptor expression by inhibiting STING and contributes to bone cancer pain in male mice |
| title_fullStr | AIM2 promotes excitatory glutamate receptor expression by inhibiting STING and contributes to bone cancer pain in male mice |
| title_full_unstemmed | AIM2 promotes excitatory glutamate receptor expression by inhibiting STING and contributes to bone cancer pain in male mice |
| title_short | AIM2 promotes excitatory glutamate receptor expression by inhibiting STING and contributes to bone cancer pain in male mice |
| title_sort | aim2 promotes excitatory glutamate receptor expression by inhibiting sting and contributes to bone cancer pain in male mice |
| topic | AIM2 STING GluN1 Spinal cord Bone cancer pain |
| url | https://doi.org/10.1038/s41598-024-83027-w |
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