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Capsaicin combined with stem cells improved mitochondrial dysfunction in PIG3V cells, an immortalized human vitiligo melanocyte cell line, by inhibiting the HSP70/TLR4/mTOR/FAK signaling axis

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Abstract

Background

Vitiligo is a common autoimmune skin disease. Capsaicin has been found to exert a positive effect on vitiligo treatment, and mesenchymal stem cells (MSCs) are also confirmed to be an ideal cell type. This study aimed to explore the influence of capsaicin combined with stem cells on the treatment of vitiligo and to confirm the molecular mechanism of capsaicin combined with stem cells in treating vitiligo.

Methods and results

PIG3V cell proliferation and apoptosis were detected using CCK-8 and TUNEL assays, MitoSOX Red fluorescence staining was used to measure the mitochondrial ROS level, and JC-1 staining was used to detect the mitochondrial membrane potential. The expression of related genes and proteins was detected using RT‒qPCR and Western blotting. Coimmunoprecipitation was used to analyze the protein interactions between HSP70 and TLR4 or between TLR4 and mTOR. The results showed higher expression of HSP70 in PIG3V cells than in PIG1 cells. The overexpression of HSP70 reduced the proliferation of PIG3V cells, promoted apoptosis, and aggravated mitochondrial dysfunction and autophagy abnormalities. The expression of HSP70 could be inhibited by capsaicin combined with MSCs, which increased the levels of Tyr, Tyrp1 and DCT, promoted the proliferation of PIG3V cells, inhibited apoptosis, activated autophagy, and improved mitochondrial dysfunction. In addition, capsaicin combined with MSCs regulated the expression of TLR4 through HSP70 and subsequently affected the mTOR/FAK signaling pathway

Conclusions

Capsaicin combined with MSCs inhibits TLR4 through HSP70, and the mTOR/FAK signaling pathway is inhibited to alleviate mitochondrial dysfunction and autophagy abnormalities in PIG3V cells.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

Not applicable.

Funding

This study was supported by the National Natural Science Foundation of China Regional Science Foundation Project [81860550].

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Author notes

  1. Yifei Wu and Xiaochuan Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, The First People’s Hospital of Yunnan Province, No. 157 Jinbi Road, Kunming, Yunnan, 650032, China

    Yifei Wu, Xiaochuan Wang, Jiayu Zhang, Zhiqiong Wang, Wenhe Zhang, Jie Xiang, Renfu Li, Jing Liu & Xin Bi

  2. Department of Laboratory, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, 650032, China

    Sha Du

  3. Department of Dermatology, Traditional Chinese Medicine Hospital of Jinggu County, Pu’er, Yunnan, 666400, China

    Jinrong Li

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  1. Yifei Wu
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Contributions

All authors contributed substantially to this manuscript. Jiayu Zhang, Sha Du and Zhiqiong Wang performed the majority of experiments and data analysis. Jinrong Li, Wenhe Zhang and Jie Xiang contributed to carrying out the experiments and interpreted the results. Renfu Li and Jing Liu helped with sample preparation. Yifei Wu and Xiaochuan Wang wrote the manuscript. Yifei Wu and Xiaochuan Wang contributed to designing the project. Xin Bi revised the manuscript, designed and conducted the project. All authors read and approved the final manuscript.

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Correspondence to Xin Bi.

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Wu, Y., Wang, X., Zhang, J. et al. Capsaicin combined with stem cells improved mitochondrial dysfunction in PIG3V cells, an immortalized human vitiligo melanocyte cell line, by inhibiting the HSP70/TLR4/mTOR/FAK signaling axis. Mol Biol Rep 51, 650 (2024). https://doi.org/10.1007/s11033-024-09592-5

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