A novel granulin homologue isolated from the jellyfish Cyanea capillata promotes proliferation and migration of human umbilical vein endothelial cells through the ERK1/2-signaling pathway
A novel granulin homologue isolated from the jellyfish Cyanea capillata promotes proliferation and migration of human umbilical vein endothelial cells through the ERK1/2-signaling pathway
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从水母 Cyanea capillata 中分离出的新型颗粒蛋白同源物通过 ERK1/2 信号通路促进人脐静脉内皮细胞的增殖和迁移
DOI：
10.1016/j.ijbiomac.2019.05.101
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Liming Zhang
中科院分区：
文献类型：
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作者：
Chao Wang;Beilei Wang;Bo Wang;Qianqian Wang;Guoyan Liu;Chongxu Fan;Liming Zhang
水母生长迅速，再生能力强，表明它们可能表达高水平的生长因子。因此，本研究的目的是从青鱼Cyanea capillata（C. capillata），并进一步探索其潜在机制。本研究首次从C. capillatatatentacles使用尺寸排阻色谱法，然后通过反相HPLC。该肽由58个氨基酸组成（MW 5782.9 Da），属于生长因子的颗粒蛋白（GRN）家族;因此，我们将其命名为Cyanea capillatagranulin-1（CcGRN-1）。第二，CCK-8法和流式细胞仪检测证实，CcGRN-1在0.5 μg/ml浓度下可促进细胞增殖，并增加细胞周期蛋白CyclinB 1和CyclinD 1的表达。第三，信号通路研究表明CcGRN-1可以激活PI 3 K/Akt和ERK 1/2 MAPK信号通路，但不能激活JNK MAPK和NF-κ B信号通路。随后，我们进一步证实CcGRN-1诱导的细胞增殖和迁移仅与ERK 1/2 MAPK信号通路相关。考虑到所有这些因素，CcGRN-1作为第一个源自水母的GRN同源物，具有促进生长的特性，可能成为在不利条件下促进人类伤口愈合的新型疗法的候选药物。
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 jellyfishCyanea capillata(C. capillata) and to further explore the underlying mechanisms. In this study, we first isolated and identified a novel polypeptide fromC. capillatatentacles 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 itCyanea capillatagranulin-1 (CcGRN-1). Second, using CCK-8 assay and flow cytometry, we verified thatCcGRN-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 thatCcGRN-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 theCcGRN-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.