Macrophage-derived netrin-1 is critical for neuroangiogenesis in endometriosis

Guo X, Xinyue Guo, Shaojie Ding, Ding S, Tiantian Li, Li T, Wang J, Jianzhang Wang, Qin Yu, Yu Q, Zhu L, Libo Zhu, Xu X, Xinxin Xu, Gen Zou, Zou G, Yangying Peng, Peng Y, Xinmei Zhang, Zhang X
International journal of biological macromolecules · 2020 · vol. 148 , pp. 226–237 · doi:10.1016/j.ijbiomac.2020.01.130 · PMID:31953174 · W2998977733
article OA: closed CC0 ⤵ 15 in-corpus citations
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Netrin-1 secreted by macrophages is essential for the development of new blood vessels in endometriosis lesions.

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Abstract

Netrin-1 is an extracellular guidance cue of neuronal navigation, mediated through interaction with its main receptors, and is known to be crucial in the development of multiple chronic inflammatory diseases. However, the expression pattern and mechanism of netrin-1 in endometriosis are currently undefined. Here we report that netrin-1 expression peaked in peritoneal macrophages found in endometriosis. Netrin-1 induced angiogenesis in ovarian endometriomas through interaction with CD146 in vascular endothelial cells. Through another receptor, neogenin, netrin-1 promoted neurite growth and sensitization in endometriosis through the up-regulation of MAP4, TAU, and CGRP. Targeted knockdown of neogenin in dorsal root ganglion (DRG) nerve cells compromised its response to netrin-1 through inhibiting phosphorylation of ERK1/2. The inhibition of netrin-1 using a neutralizing antibody reduced vascular and nerve infiltration in rat endometriotic lesions. In summary, our results suggest that netrin-1 is an important factor that promotes neuroangiogenesis in endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Macrophages Neovascularization, Pathologic Netrin-1 Animals Cells, Cultured Endometriosis Endothelial Cells Endothelial Cells Female Ganglia, Spinal Ganglia, Spinal Humans Macrophages MAP Kinase Signaling System MAP Kinase Signaling System Membrane Proteins Membrane Proteins Neovascularization, Pathologic Netrin-1

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