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Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) -derived Peptide MPAPO Stimulates Adipogenic Differentiation by Regulating the Early Stage of Adipogenesis and ERK Signaling Pathway

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Abstract

Regenerative medicine and tissue engineering have delivered new healing possibilities to the treatment of soft tissue defects, but the selection of seed cells is critical for treatment. Adipose-derived stem cells have perpetually been a preferred candidate for seed cells due to their wealthy sources, simple access, high plasticity, and powerful value-added capabilities. How to improve the efficiency of adipogenic differentiation is the key to the treatment. Pituitary adenylate cyclase-activating peptide, as a biologically active peptide secreted by the pituitary, is widely involved in regulating the body’s sugar metabolism and lipid metabolism. However, the effects of MPAPO in ADSCs adipogenic differentiation remain unknown. Our results reveal that MPAPO treatment improves the adipogenic differentiation efficiency of ADSCs, including promoting the accumulation of lipid droplets and triglycerides, and the expression of adipocyte protein biomarkers PPARγ and C/EBPa. Additionally, the mechanism studies showed that the effective window of MPAPO-induced adipogenesis was the first 3 days during ADSCs differentiation. MPAPO selectively binds to the PAC1 receptor and promotes adipogenic differentiation of ADSCs by activating the ERK signaling pathway and elevating cell proliferation during postconfluent mitosis stage. Altogether, we demonstrate that MPAPO plays a crucial role in ADSCs adipogenesis, providing experimental basis and data for exploring therapeutic options in tissue defect repair.

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The data used to support the findings of this study are available from every author upon request.

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Acknowledgements

I would like to thank all the students in the lab for their help and the members of the research group for their efforts. I would also like to thank for the funding supports of the National Natural Science Foundation of China (No. 82073748 and 81741130); the Guang-dong Basic and Applied Basic Research Foundation (No. 2019A1515011866 and 2021A1515010993); Guang-dong Science and Technology Innovation Strategy Special fund (International science and technology cooperation projects, No. 2021A0505030034).

Funding

This study was supported by the National Natural Science Foundation of China (No. 82073748 and 81741130); the Guang-dong Basic and Applied Basic Research Foundation (No. 2019A1515011866 and 2021A1515010993); Guang-dong Science and Technology Innovation Strategy Special fund (International science and technology cooperation projects, No. 2021A0505030034).

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Authors and Affiliations

  1. Department of Cellular Biology, Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China

    Zixian Wang, Jianmin Liu, Yongmei Huang, Qian Liu, Meng Chen, Chunyan Ji, Jia Feng & Yi Ma

  2. Department of Cellular Biology, Institute of Biomedicine, Jinan University, 601 Huangpu Avenue West, 510632, Guangzhou, China

    Yi Ma

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Zixian Wang and Yi Ma contributed to the conception; Zixian Wang and Jianmin Liu carried out the experiments; Zixian Wang, Jianmin Liu, Yongmei Huang, Qian Liu, Meng Chen, and Yi Ma contributed to data or analysis tools and performed the analysis; Zixian Wang, Jianmin Liu, Qian Liu, Chunyan Ji, Meng Chen, and Yi Ma reviewed the articles and wrote the original draft; Zixian Wang, Yongmei Huang, Jia Feng, and Yi Ma contributed to the manuscript revision and editing; All the authors read and approved the submitted version.

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Wang, Z., Liu, J., Huang, Y. et al. Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) -derived Peptide MPAPO Stimulates Adipogenic Differentiation by Regulating the Early Stage of Adipogenesis and ERK Signaling Pathway. Stem Cell Rev and Rep 19, 516–530 (2023). https://doi.org/10.1007/s12015-022-10415-y

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