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P311 knockdown alleviates hyperoxia-induced injury by inactivating the Smad3 signaling pathway in type II alveolar epithelial cells

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Abstract

P311 is associated with alveolar formation and development. However, the role and possible mechanism of P311 in hyperoxia-induced injury in type II alveolar epithelial cells (AEC II) need to be elucidated. In our study, rat AEC II (RLE-6TN) were exposure to normoxia (21% O2 and 5% CO2) or hyperoxia (95% O2 and 5% CO2) for 24 h, followed by determination of P311 expression. After knockdown of P311 and hyperoxic treatment, cell viability, cell cycle progression, apoptosis and the Smad3 signaling pathway were examined. Rat AEC II were pretreated with SIS3 HCl for 4 h and then subjected to P311 overexpression plasmid transfection and hyperoxic exposure. Then, cell viability, apoptosis and the Smad3 signaling pathway were determined. The results showed that hyperoxic exposure significantly elevated P311 levels in rat AEC II. P311 knockdown increased cell viability, accelerated cell cycle progression and inhibited apoptosis, as well as suppression of the Smad3 signaling pathway in hyperoxia-exposed AEC II. Additionally, we found that P311 overexpression enhanced the effects of hyperoxia. Interestingly, SIS3 HCl incubation blocked the effects of P311 overexpression on rat AEC II function under hyperoxic condition, as evidenced by an increase in cell viability, and suppressions of apoptosis and the Smad3 signaling pathway. These results indicate that P311 knockdown may ameliorate hyperoxia-induced injury by inhibiting the Smad3 signaling pathway in rat AEC II. P311 may be a novel target for the treatment of hyperoxia-induced lung injury and even bronchopulmonary dysplasia (BPD).

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Funding

This work was supported by National Natural Science Foundation of China under Grant Number 81560256.

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  1. Jun Jiang and Juan Wang these authors have contributed equally.

Authors and Affiliations

  1. Department of Pediatric Intensive Care Unit, Guizhou Provincial People’s Hospital, 83 Zhongshan East Road, Guiyang, 550002, Guizhou, China

    Jun Jiang, Cen Li, Lianqin Mo & Dong Huang

  2. Department of Pediatrics, Affiliated Hospital of Hebei University, Handan, China

    Juan Wang

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  1. Jun Jiang
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HD designed the study and wrote the manuscript. JJ and HD analyzed the data. WJ, LC, MLQ and HD performed the experiments. All authors read and approved the final manuscript.

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Correspondence to Dong Huang.

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Jiang, J., Wang, J., Li, C. et al. P311 knockdown alleviates hyperoxia-induced injury by inactivating the Smad3 signaling pathway in type II alveolar epithelial cells. Mol Cell Biochem 478, 277–284 (2023). https://doi.org/10.1007/s11010-022-04500-6

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