A novel granulin homologue isolated from the jellyfish Cyanea capillata that promotes proliferation and migaration of human umbilical vein endothelial cells through the ERK1/2 signaling pathway

• DOI: 10.1016/j.toxicon.2018.10.084
• Publication Date: 2019-01-30T09:22:07Z
• Authors: Beilei Wang; Chao Wang; Bo Wang; Qianqian Wang; Guoyan Liu; Chongxu Fan; Liming Zhang
• Keywords: Fish Proteins; 0301 basic medicine; Wound Healing; Scyphozoa; Cell Survival; MAP Kinase Signaling System; Cell Cycle; 03 medical and health sciences; Cell Movement; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Human Umbilical Vein Endothelial Cells; Animals; Humans; Amino Acid Sequence; Peptides; Cell Proliferation; Granulins

Jellyfish grow rapidly and have a strong regenerative ability, indicating that they may express high levels of growth factors. Therefore, the aim of this research was to isolate the growth-promoting components from the jellyfish Cyanea capillata (C. capillata) and to further explore the underlying mechanisms. In this study, we first isolated and identified a novel polypeptide from C. capillata tentacles using size-exclusion chromatography followed by reverse-phase HPLC. This peptide, consisting of 58 amino acids (MW 5782.9 Da), belonged to the granulin (GRN) family of growth factors; thus, we named it Cyanea capillata granulin-1 (CcGRN-1). Second, using CCK-8 assay and flow cytometry, we verified that CcGRN-1 at the 0.5 μg/ml concentration could promote cell proliferation and increase the expression of cell-cycle proteins (CyclinB1 and CyclinD1). Third, signaling pathways studies showed that CcGRN-1 could activate the PI3K/Akt- and ERK1/2 MAPK-signaling pathways but not the JNK MAPK- or NF-κB-signaling pathways. Subsequently, we further confirmed that the CcGRN-1-induced cell proliferation and migration were associated only with the ERK1/2 MAPK-signaling pathway. Considering all of these factors, CcGRN-1, as the first jellyfish-derived GRN homologue, possesses growth-promoting properties and may be a candidate for novel therapeutics to promote human wound healing in unfavorable conditions.