Int J Biol Sci
2024; 20(7):2507-2531.
doi:10.7150/ijbs.94548 This issueCite
Research Paper
Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway
Jing Lan, Ziteng Deng, Qiuzhen Wang, Dan Li, Kai Fan, Jianyu Chang, Yunfei Ma✉
State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
✉ Corresponding author: College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China; E-mail address: yunfeimaedu.cn (Yunfei Ma).
Citation:
Lan J, Deng Z, Wang Q, Li D, Fan K, Chang J, Ma Y. Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway. Int J Biol Sci 2024; 20(7):2507-2531. doi:10.7150/ijbs.94548. https://www.ijbs.com/v20p2507.htm
Neuropeptide substance P (SP) belongs to a family of bioactive peptides and regulates many human diseases. This study aims to investigate the role and underlying mechanisms of SP in colitis. Here, activated SP-positive neurons and increased SP expression were observed in dextran sodium sulfate (DSS)-induced colitis lesions in mice. Administration of exogenous SP efficiently ameliorated the clinical symptoms, impaired intestinal barrier function, and inflammatory response. Mechanistically, SP protected mitochondria from damage caused by DSS or TNF-α exposure, preventing mitochondrial DNA (mtDNA) leakage into the cytoplasm, thereby inhibiting the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. SP can also directly prevent STING phosphorylation through the neurokinin-1 receptor (NK1R), thereby inhibiting the activation of the TBK1-IRF3 signaling pathway. Further studies revealed that SP alleviated the DSS or TNF-α-induced ferroptosis process, which was associated with repressing the cGAS-STING signaling pathway. Notably, we identified that the NK1R inhibition reversed the effects of SP on inflammation and ferroptosis via the cGAS-STING pathway. Collectively, we unveil that SP attenuates inflammation and ferroptosis via suppressing the mtDNA-cGAS-STING or directly acting on the STING pathway, contributing to improving colitis in an NK1R-dependent manner. These findings provide a novel mechanism of SP regulating ulcerative colitis (UC) disease.
Lan, J., Deng, Z., Wang, Q., Li, D., Fan, K., Chang, J., Ma, Y. (2024). Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway. International Journal of Biological Sciences, 20(7), 2507-2531. https://doi.org/10.7150/ijbs.94548.
ACS
Lan, J.; Deng, Z.; Wang, Q.; Li, D.; Fan, K.; Chang, J.; Ma, Y. Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway. Int. J. Biol. Sci. 2024, 20 (7), 2507-2531. DOI: 10.7150/ijbs.94548.
NLM
Lan J, Deng Z, Wang Q, Li D, Fan K, Chang J, Ma Y. Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway. Int J Biol Sci 2024; 20(7):2507-2531. doi:10.7150/ijbs.94548. https://www.ijbs.com/v20p2507.htm
CSE
Lan J, Deng Z, Wang Q, Li D, Fan K, Chang J, Ma Y. 2024. Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway. Int J Biol Sci. 20(7):2507-2531.
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