Protective effects and molecular mechanisms of Achyranthes bidentata polypeptide k on Schwann cells

Ann Transl Med. 2021 Mar;9(5):381. doi: 10.21037/atm-20-2900.

Abstract

Background: Achyranthes bidentata polypeptide k (ABPPk) is an active ingredient used in traditional Chinese medicine separated from Achyranthes bidentata polypeptides. So far, the role of ABPPk in peripheral nerve protection has not been comprehensively studied.

Methods: In this study, primary Schwann cells exposed to serum deprivation were treated with ABPPk or nerve growth factor (NGF) in vitro. Cell viability, cell apoptosis, apoptosis-related protein expression, and antioxidant enzyme activity were analyzed. To further explore the underlying molecular mechanisms and key regulatory molecules involved in the effects of ABPPk, integrative and dynamic bioinformatics analysis at different time points was carried out following RNA-seq of Schwann cells subjected to serum deprivation.

Results: We found that ABPPk could effectively reduce Schwann cell apoptosis caused by serum deprivation, which was comparable to NGF's anti-apoptotic effects. ABPPk had the largest number of upregulated and downregulated differential expression genes at the earliest 0.5 h time, while NGF had fewer differential expression genes at this early stage. The significant difference at this time point between the two groups was also displayed in heatmaps. The molecular regulation of diseases and functions and canonical pathways revealed that ABPPk had more participation and advantages in the vasculature and immune system areas, especially angiogenesis regulation. Also, ABPPk demonstrated an earlier start in these molecular regulations than NGF. Furthermore, the analysis of transcription factors also illustrated that ABPPk not only had more key initial regulatory factors participating in vascular-related processes, but these also remained for a longer period. There was no significant difference in neural-related molecular regulation between the two groups.

Conclusions: Using high-throughput sequencing technology, our work unveiled the protective effects of ABPPk on Schwann cells after serum deprivation in a more comprehensive manner. These results further enrich the positive functions and molecular mechanisms of ABPPk and traditional Chinese medicine and benefit the discovery of novel therapeutic targets for peripheral nerve regeneration.

Keywords: Achyranthes bidentata polypeptide k (ABPPk); Schwann cells (SCs); blood vessel; cell apoptosis; molecular mechanism.