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| S100A6 Promotes Angiogenesis Through Recruiting and Activating Macrophages |
LIN Lu,HU Li-jun,HUANG Yi-yun,CHEN Lu,HUANG Mao,PENG Qi,HU Qin,ZHOU Lan( ) |
| Key Laboratory of Laboratory Medical Diagnostic of Ministry of Education Chongqing Medical University, Chongqing 400016, China |
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Abstract Objective: To investigate the effect of S100A6 in microenvironment on promoting angiogenesis via macrophages and the underlying mechanism. Methods: (1)Macrophages were treated by recombinant proteins GST-hS100A6: ①Conditioned medium was collected (named A6-Mφ-CM) to resuspend human umbilical vein endothelial cells (HUVEC), and the effect on angiogenesis was examined by in vitro endothelial capillary formation assay. ②The mRNA and protein levels of CD163, CCL2, IL-6, VEGFA in macrophages were evaluated by Real-time PCR and Western blot. And JAK2 and STAT3 and their phosphorylation levels in macrophages were detected by Western blot. ③ The migration ability of macrophages was detected by Transwell migration assay. (2)The change of macrophage migration ability was detected by Transwell assay after pre-treatment of JAK2 inhibitor XL019. Results: (1) A6-Mφ-CM had obvious effects on promoting angiogenesis,the number of branches and branch length of the A6-Mφ-CM group was significantly higher than that of the GST-Mφ-CM group (P<0.05; P<0.05), and was also significantly higher than that of GST-hS100A6 group, suggesting that S100A6 treated macrophages can promote angiogenesis, while S100A6 has no direct pro-angiogenic effect. (2) After treatment with GST-hS100A6, the mRNA and protein levels of CD163, CCL2, IL-6 and VEGFA in macrophages were up-regulated compared with GST group (P<0.05; P<0.05; P<0.05; P<0.05), suggesting that S100A6 induced polarization of macrophages into a pro-angiogenic phenotype. (3) The number macrophage migrated in GST-hS100A6 group was 1.4-fold as much as that in GST group (P<0.01), suggesting that S100A6 can enhance macrophage migration. (4) GST-hS100A6 upregulated the levels of JAK2, STAT3 and their phosphorylation proteins in macrophages, indicating that JAK2/STAT3 pathway of macrophages was activated. (5) The effect of GST-hS100A6 on promoting macrophage migration was partly inhibited by JAK2 inhibitor XL019(P<0.01). Conclusion: S100A6 in the microenvironment can recruit macrophages by activating JAK2/STAT3 signaling, and further induce macrophage into a pro-angiogenic phenotype to promote angiogenesis indirectly.
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Received: 29 October 2019
Published: 02 June 2020
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Corresponding Authors:
Lan ZHOU
E-mail: zhoulan@cqmu.edu.cn
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