A potent peptide as adiponectin receptor 1 agonist to against fibrosis
Autor: | Lingman Ma, Zhen Zhang, Xiaowen Xue, Yumeng Wan, Boping Ye, Kejiang Lin |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: | |
Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 32, Iss 1, Pp 624-631 (2017) |
Druh dokumentu: | article |
ISSN: | 1475-6366 1475-6374 14756366 |
DOI: | 10.1080/14756366.2017.1284067 |
Popis: | 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. |
Databáze: | Directory of Open Access Journals |
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