A potent peptide as adiponectin receptor 1 agonist to against fibrosis

Abstract

Fibrotic diseases have become a major cause of death in the developed world. AdipoR1 agonists are potent inhibitors of fibrotic responses. Here, we focused on the in silico identification of novel AdipoR1 peptide agonists. A homology model was constructed to predict the 3D structure of AdipoR1. By docking to known active peptides, the putative active site of the model was further explored. A virtual screening study was then carried out with a set of manually designed peptides using molecular docking. Peptides with high docking scores were then evaluated for their anti-fibrotic properties. The data indicated that the novel peptide Pep70 significantly inhibited the proliferation of hepatic stellate cells (HSC) and NIH-3T3 cells (18.33% and 27.80%) and resulted in favouring cell-cycle arrest through increasing the accumulation of cells in the G0/G1 phase by 17.08% and 15.86%, thereby reducing the cell population in the G2/M phase by 11.25% and 15.95%, respectively. Additionally, Pep70 exhibited the most marked suppression on the expression of α-smooth muscle actin (α-SMA), collagen type I alpha1 (COL1A1) and TGF-β1. Therefore, the peptide Pep70 was ultimately identified as an inhibitor of fibrotic responses and as a potential AdipoR1 agonist.

Keywords:

• adiponectin receptor 1
• homology modelling
• molecular docking
• virtual screening
• anti-fibrotic activity

Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (No. 81573348).

Disclosure statement

The authors report no conflicts of interest.

Compliance with ethical standards

None human participants or animals were involved in our studies.

Additional information

Funding

This work was supported by a grant from the National Natural Science Foundation of China (No. 81573348).