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

Guo, Xinyue; Ding, Shaojie; Li, Tiantian; Wang, Jianzhang; Qin, Yu; Zhu, Libo; Xu, Xinxin; Zou, Gen; Peng, Yangying; Zhang, Xinmei

doi:10.1016/j.ijbiomac.2020.01.130

Cited by 20 publications

(17 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Last but not least, we have not studied the effects of netrin-1 on different receptors; that is, how netrin-1 causes endometriosis-associated pain. In another study, we demonstrated that netrin-1 induced angiogenesis in ovarian endometriomas through interaction with CD146 in vascular endothelial cells and promoted neurite growth and sensitization through another receptor, neogenin (76). This is an ongoing study, and we will further validate and inform our research with additional animal experiments.…”

Section: A B C D E F G H Imentioning

confidence: 63%

Macrophage-derived netrin-1 contributes to endometriosis- associated pain

Ding¹,

Guo²,

Zhu³

et al. 2021

Ann Transl Med

Self Cite

View full text Add to dashboard Cite

Background: Endometriosis-associated pain can be considered a type of neuropathic pain. Netrin-1 is an axon guidance cue that regulates axonal attraction or rejection in neural injury and regeneration. However, whether netrin-1 plays a role in endometriosis-associated pain remains unclear. This study aimed to determine the role of netrin-1 in endometriosis-related pain. Methods: Peripheral blood, peritoneal fluid, and endometrial tissues were sampled from women with (n=37) and without endometriosis (n=23). Lipopolysaccharide (LPS) and interferon gamma (IFN-γ) were used to stimulate human monocytic cell lines (THP-1) and rat alveolar macrophage-derived cell lines (NR8383) to induce M1 phenotype macrophages. Serum netrin-1 concentrations, endometrial expression levels of netrin-1, and its receptors including deleted in colorectal cancer (DCC), A2B adenosine receptor (A2BAR), uncoordinated B receptor (UNC5B), uncoordinated C receptor (UNC5C) and Down's syndrome cell adhesion molecule (DSCAM) were assessed. The polarization phenotypes of the peritoneal macrophages were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry. The expression levels of M1 markers and netrin-1 in THP-1/NR8383 cells were determined.Results: The expression levels of netrin-1 in serum and endometriotic lesions were significantly higher in women with endometriosis, and were positively correlated with the severity of endometriosis-associated pain.Netrin-1 was co-expressed with CD68 (a macrophage marker) in endometriotic lesions and was synthesized and secreted by THP-1 and NR8383 cells in the process of M1 polarization. In women with endometriosis, peritoneal macrophages were polarized towards the M1 phenotype. In addition, increased expression of DCC and A2BAR, and decreased expression of UNC5B, UNC5C and DSCAM were found in endometriotic lesions.Conclusions: These results suggest that netrin-1 production by macrophages in endometriotic lesions may play an important role in endometriosis-associated pain.

show abstract

Section: A B C D E F G H Imentioning

confidence: 63%

Macrophage-derived netrin-1 contributes to endometriosis- associated pain

Ding¹,

Guo²,

Zhu³

et al. 2021

Ann Transl Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…Resident synovial macrophages provide a protective barrier for the joint 19 , and recent studies have identified macrophage-derived Netrin-1. Macrophage-derived Netrin-1 is critical for neuroangiogenesis in endometriosis 20 and plays a role in vascular diseases 21 . The upregulated expression of Netrin-1 is likely caused by synovial inflammation, which destroys the macrophage barrier in the lining layer of the synovial membrane, and then synovial macrophages secrete Netrin-1, which causes subsequent development of inflammation.…”

Section: Discussionmentioning

confidence: 99%

The expression of Netrin-1 in the MIA-induced osteoarthritic temporomandibular joint in mice

Xiao

Jiang

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Subchondral bone degeneration is the main pathological change during temporomandibular joint (TMJ) osteoarthritis (OA) development. Netrin-1, an axon-guiding factor, might play roles in OA development and pain. The purpose of this study was to investigate the expression of Netrin-1 in TMJ OA and its possible role in the progression of TMJ OA and pain. The synovial fluids of temporomandibular joint disorders (TMDs) patients were collected for Netrin-1 by enzyme linked immunosorbent assay (ELISA). TMJ OA model was built by MIA joint injection, and then the von Frey test, hematoxylin & eosin (H&E) staining, toluidine blue (TB) staining, immunohistochemical (IHC) staining and micro-CT were performed. After induction of osteoclast differentiation of raw264.7 cells, immunofluorescence (IF) was used to detect the Netrin-1 and its receptors on osteoclast membrane. The concentration of Netrin-1 increased in the synovial fluid of TMJ OA patients. After MIA injection to TMJ, the head withdrawal threshold (HWT) was significantly decreased. Microscopically, the structural disorder of subchondral bone was the most obvious at the 2nd week after MIA injection. In addition, Netrin-1 expression increased in the subchondral bone at the 2nd week after MIA injection. In vitro, the expressions of Netrin-1 and its receptor Unc5B were upregulated on the osteoclast membrane. Netrin-1 might be an important regulator during bone degeneration and pain in the process of TMJ OA.

show abstract

“…Resident synovial macrophages provide a protective barrier for the joint 11 , and recent studies have identi ed macrophage-derived Netrin-1. Macrophage-derived Netrin-1 is critical for neuroangiogenesis in endometriosis 12 and plays a role in vascular diseases 13 . The upregulated expression of Netrin-1 is likely caused by synovial in ammation, which destroys the macrophage barrier in the lining layer of the synovial membrane, and then synovial macrophages secrete Netrin-1, which causes subsequent development of in ammation.…”

Section: Discussionmentioning

confidence: 99%

The Expression of Netrin-1 in the Osteoarthritic Temporomandibular Joint

Xiao

Jiang

et al. 2021

Preprint

View full text Add to dashboard Cite

Subchondral bone degeneration is the main pathological change during temporomandibular joint (TMJ) osteoarthritis (OA) development. Netrin-1, an axon-guiding factor, might play roles in OA development and pain. The purpose of this study was to investigate the expression of Netrin-1 in TMJ OA and its possible role in the progression of TMJ OA and pain. The content of Netrin-1 in the synovial fluid of temporomandibular joint disorders (TMDs) patients was detected by ELISA. After injection of MIA into the TMJ animal model, hematoxylin & eosin (H&E) staining, toluidine blue (TB) staining and micro-CT were performed to detect the change of TMJ. Netrin-1 expression in the condyle was detected by immunohistochemical (IHC) staining. The pain experience was examined by the von Frey test in animal model. The concentration of Netrin-1 increased in the synovial fluid of TMJ OA patients with the VAS scores increased. In the TMJ OA model, the structural disorder of subchondral bone was the most obvious at the 2nd week. In addition, the head withdrawal threshold (HWT) was significantly decreased in the TMJ OA model. Netrin-1 expression increased in the subchondral bone at the 2nd week after MIA injection in the mouse TMJ. Cultivate raw264.7 cells and induce them to differentiate into osteoclasts. Netrin-1 and its receptor Unc5B are detected to be expressed on the osteoclast membrane. Thus, Netrin-1 might be a regulator during degeneration and pain in the process of TMJ OA.

show abstract

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

Cited by 20 publications

References 54 publications

Macrophage-derived netrin-1 contributes to endometriosis- associated pain

Macrophage-derived netrin-1 contributes to endometriosis- associated pain

The expression of Netrin-1 in the MIA-induced osteoarthritic temporomandibular joint in mice

The Expression of Netrin-1 in the Osteoarthritic Temporomandibular Joint

Contact Info

Product

Resources

About