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Sesamin Induces the Transdifferentiation of Type II Alveolar Epithelial Cells via AnnexinA1 and TRPV1

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Abstract

Purpose

Acute lung injury (ALI) with high rates of morbidity is often accompanied by the apoptosis in the type I alveolar epithelial cells (ATIs). Thus, the transdifferentiation of type II alveolar epithelial cells (ATIIs) into ATIs is crucial for the maintenance of alveolar epithelial functions. We aimed to elucidate the role of sesamin in the transdifferentiation of ATIIs to ATIs and the involvement of the TRPV1/AKT pathway.

Methods

In vivo, the mouse model of ALI was simulated by intraperitoneal and intratracheal injections of lipopolysaccharide (LPS), respectively. The protective effects of sesamin on ALI were investigated using the survival rate, lung/body weight ratio, histological analysis of lung with HE staining, and mRNA levels of inflammatory factors. Western blot analysis and immunofluorescence detection of ATIs marker AQP5 were used to evaluate the protective effect of sesamin on ATIs. Western blot, EdU, and qPCR analyses were applied to detect changes in apoptosis, proliferation, and transdifferentiation markers of ATII A549 cell lines. Small interfering RNA (siRNA) was used to detect the involvement and relationships between the sesamin receptors (ANXA1 and TRPV1) and the AKT pathway in transdifferentiation.

Results

Sesamin (200 mg/kg) significantly improved LPS-induced ALI and inhibited LPS-induced ATIs reduction. A low concentration of sesamin (20 μM) promoted the transdifferentiation of ATIIs to ATIs. Both ANXA1 and TRPV1 were involved in sesamin-promoted transdifferentiation, while the P-AKT (S473) level was down-regulated by TRPV1 siRNA.

Conclusion

Sesamin may promote transdifferentiation of ATII to ATI to ultimately rescue ALI, with TRPV1/AKT pathway involved in this transdifferentiation. This study revealed a novel role of sesamin in promoting the transdifferentiation of ATIIs to ATIs, providing experimental supports for the potential targets of ALI therapy.

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Abbreviations

AKT:

Protein kinase B

ALI:

Acute lung injury

ANXA1:

Annexin A1

AQP5:

Aquaporin-5

ATIs:

Type I alveolar epithelial cells

ATIIs:

Type II alveolar epithelial cells

CFTR:

Cystic fibrosis transmembrane regulator

DMSO:

Dimethyl sulfoxide

LPS:

Lipopolysaccharide

PDPN:

Podoplanin

RAGE:

Advanced glycosylation end product-specific receptor

SFTPC:

Surfactant protein C

TRPV1:

Transient receptor potential vanilloid 1

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Acknowledgements

We thank Sen Wang, Haiyan Yu, Xiaomin Zhao, Yuyu Guo at the State Key Laboratory of Microbial Technology, Shandong University, for the assistance in microimaging of fluorescence microscope analysis.

Funding

This work was supported by the project of Shandong Shilixiang Sesame Products Co., Ltd.

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Author notes

  1. Jiaojiao Zhang and Jinrun Zhou have contributed equally to this work.

Authors and Affiliations

  1. Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, 266237, People’s Republic of China

    Jiaojiao Zhang, Jinrun Zhou, Yifan Yu, Yuqing Cai, Zhiliang Li, Yao Lu & Jing Zhao

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  1. Jiaojiao Zhang
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  2. Jinrun Zhou
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  3. Yifan Yu
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  4. Yuqing Cai
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  6. Yao Lu
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  7. Jing Zhao
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Contributions

The study was designed by JZ. JZ, JZ, and YY carried out the experiments. YC, ZL, and YL analyzed the data. JZ and JZ wrote the first draft of this manuscript. JZ and JZ finalized the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jing Zhao.

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Zhang, J., Zhou, J., Yu, Y. et al. Sesamin Induces the Transdifferentiation of Type II Alveolar Epithelial Cells via AnnexinA1 and TRPV1. Lung 201, 65–77 (2023). https://doi.org/10.1007/s00408-023-00598-7

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  • DOI: https://doi.org/10.1007/s00408-023-00598-7

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