Activation of AMPK in platelets promotes the production of offspring

Abstract

Platelets are terminally differentiated anucleated cells, but they still have cell-like functions and can even produce progeny platelets. However, the mechanism of platelet sprouting has not been elucidated so far. Here, we show that when platelet-rich plasma(PRP) was cultured at 37°C, platelets showed a spore phenomenon. The number of platelets increased when given a specific shear force. It is found that AMP-related signaling pathways, such as PKA and AMPK are activated in platelets in the spore state. Meanwhile, the mRNA expression levels of genes, such as CNN3, CAPZB, DBNL, KRT19, and ESPN related to PLS1 skeleton proteins also changed. Moreover, when we use the AMPK activator AICAR(AI) to treat washed platelets, cultured platelets can still appear spore phenomenon. We further demonstrate that washed platelets treated with Forskolin, an activator of PKA, not only platelet sprouting after culture but also the AMPK is activated. Taken together, these data demonstrate that AMPK plays a key role in the process of platelet budding and proliferation, suggesting a novel strategy to solve the problem of clinical platelet shortage.

Plain Language Summary

What is new?

• In this study, we showed that when platelet-rich plasma(PRP) was cultured at 37°C, platelets showed spore phenomenon and increased.

• It was found that AMP-related signaling pathways, such as PKA and AMPK were activated in platelets in the spore state.

• In addition, we found that PKA acts as an upstream kinase of AMPK.

• In the process of platelet sprouting and proliferation, the mRNA expression levels of skeleton protein PLS1 and its related genes, such as CNN3, CAPZB, DBNL, KRT19, andESPN also changed.

What is the impact?

• Our study proposes a new strategy to solve the problem of clinical platelet shortage.

Keywords:

• AMPK
• PKA
• platelet-rich plasma
• PLS1

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

T. Z designed and performed the experiments, analyzed data, and wrote the manuscript. M.Y and S.L helped revise the paper. R. Y and K.D. initiated and supervised the project, designed research, analyzed and interpreted results, and wrote the paper. All authors reviewed the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/09537104.2024.2334701

Additional information

Funding

This work was supported by grants from the Key Projects of the National Natural Science Foundation of China [82230003 to K.D.], the Key International Cooperation Projects of the National Natural Science Foundation of China [81820108003 to K.D.], National 455 Natural Science Foundation of China [81770117 to K.D.].