Inhibition of calcineurin/NFATc4 signaling attenuates ventilator‑induced lung injury

Li,Min; Fang,Xiang‑Zhi; Liu,Xiao‑Tian; Zheng,Yong‑Feng; Xie,Yun‑Bin; Ma,Xiao‑Dong; Xia,Yan; Shao,Dong‑Hua

doi:10.3892/mmr.2019.10851

Inhibition of calcineurin/NFATc4 signaling attenuates ventilator‑induced lung injury

Authors:
- Min Li
- Xiang‑Zhi Fang
- Xiao‑Tian Liu
- Yong‑Feng Zheng
- Yun‑Bin Xie
- Xiao‑Dong Ma
- Yan Xia
- Dong‑Hua Shao
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Affiliations: Department of Anesthesiology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China, Department of Anesthesiology, Clinical Medical School of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, P.R. China
Published online on: November 26, 2019 https://doi.org/10.3892/mmr.2019.10851
Pages: 607-614
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ventilator‑induced lung injury (VILI) is a life‑threatening condition caused by the inappropriate use of mechanical ventilation (MV). However, the precise molecular mechanism inducing the development of VILI remains to be elucidated. In the present study, it was revealed that the calcineurin/NFATc4 signaling pathway mediates the expression of adhesion molecules and proinflammatory cytokines essential for the development of VILI. The present results revealed that a high tidal volume ventilation (HV) caused lung inflammation and edema in the alveolar walls and the infiltration of inflammatory cells. The calcineurin activity and protein expression in the lungs were increased in animals with VILI, and NFATc4 translocated into the nucleus following calcineurin activation. Furthermore, the translocation of NFATc4 and lung injury were prevented by a calcineurin inhibitor (CsA). Thus, the present results highlighted the critical role of the calcineurin/NFATc4 signaling pathway in VILI and suggest that this pathway coincides with the release of ICAM‑1, VCAM‑1, TNF‑α and IL‑1β.

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