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Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2+ axis

  • Authors:
    • Jun-Hui Li
    • Han-Xing Wan
    • Li-Hong Wu
    • Fang Fang
    • Jian-Xin Wang
    • Hui Dong
    • Feng Xu
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing 400037, P.R. China, Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, Qingdao, Shandong 266073, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 110
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    Published online on: May 1, 2024
       https://doi.org/10.3892/mmr.2024.13234
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Abstract

Although exogenous calcitonin gene‑related peptide (CGRP) protects against hyperoxia‑induced lung injury (HILI), the underlying mechanisms remain unclear. The present study attempted to elucidate the molecular mechanism by which CGRP protects against hyperoxia‑induced alveolar cell injury. Human alveolar A549 cells were treated with 95% hyperoxia to establish a hyperoxic cell injury model. ELISA was performed to detect the CGRP secretion. Immunofluorescence, quantitative (q)PCR, and western blotting were used to detect the expression and localization of CGRP receptor (CGRPR) and transient receptor potential vanilloid 1 (TRPV1). Cell counting kit‑8 and flow cytometry were used to examine the proliferation and apoptosis of treated cells. Digital calcium imaging and patch clamp were used to analyze the changes in intracellular Ca2+ signaling and membrane currents induced by CGRP in A549 cells. The mRNA and protein expression levels of Cyclin D1, proliferating cell nuclear antigen (PCNA), Bcl‑2 and Bax were detected by qPCR and western blotting. The expression levels of CGRPR and TRPV1 in A549 cells were significantly downregulated by hyperoxic treatment, but there was no significant difference in CGRP release between cells cultured under normal air and hyperoxic conditions. CGRP promoted cell proliferation and inhibited apoptosis in hyperoxia, but selective inhibitors of CGRPR and TRPV1 channels could effectively attenuate these effects; TRPV1 knockdown also attenuated this effect. CGRP induced Ca2+ entry via the TRPV1 channels and enhanced the membrane non‑selective currents through TRPV1 channels. The CGRP‑induced increase in intracellular Ca2+ was reduced by inhibiting the phospholipase C (PLC)/protein kinase C (PKC) pathway. Moreover, PLC and PKC inhibitors attenuated the effects of CGRP in promoting cell proliferation and inhibiting apoptosis. In conclusion, exogenous CGRP acted by inversely regulating the function of TRPV1 channels in alveolar cells. Importantly, CGRP protected alveolar cells from hyperoxia‑induced injury via the CGRPR/TRPV1/Ca2+ axis, which may be a potential target for the prevention and treatment of the HILI.
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Copy and paste a formatted citation
Spandidos Publications style
Li J, Wan H, Wu L, Fang F, Wang J, Dong H and Xu F: Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2<sup>+</sup> axis. Mol Med Rep 30: 110, 2024.
APA
Li, J., Wan, H., Wu, L., Fang, F., Wang, J., Dong, H., & Xu, F. (2024). Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2<sup>+</sup> axis. Molecular Medicine Reports, 30, 110. https://doi.org/10.3892/mmr.2024.13234
MLA
Li, J., Wan, H., Wu, L., Fang, F., Wang, J., Dong, H., Xu, F."Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2<sup>+</sup> axis". Molecular Medicine Reports 30.1 (2024): 110.
Chicago
Li, J., Wan, H., Wu, L., Fang, F., Wang, J., Dong, H., Xu, F."Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2<sup>+</sup> axis". Molecular Medicine Reports 30, no. 1 (2024): 110. https://doi.org/10.3892/mmr.2024.13234
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Wan H, Wu L, Fang F, Wang J, Dong H and Xu F: Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2<sup>+</sup> axis. Mol Med Rep 30: 110, 2024.
APA
Li, J., Wan, H., Wu, L., Fang, F., Wang, J., Dong, H., & Xu, F. (2024). Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2<sup>+</sup> axis. Molecular Medicine Reports, 30, 110. https://doi.org/10.3892/mmr.2024.13234
MLA
Li, J., Wan, H., Wu, L., Fang, F., Wang, J., Dong, H., Xu, F."Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2<sup>+</sup> axis". Molecular Medicine Reports 30.1 (2024): 110.
Chicago
Li, J., Wan, H., Wu, L., Fang, F., Wang, J., Dong, H., Xu, F."Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2<sup>+</sup> axis". Molecular Medicine Reports 30, no. 1 (2024): 110. https://doi.org/10.3892/mmr.2024.13234
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