Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.686886
Keywords
PDGF-D; C1qa; C3; macrophage polarization; inflammation
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Funding
- National Natural Science Foundation of China [81670855]
- Key Program of Guangzhou Scientific Research Plan [201804020010]
- Key Research and Development Plan of Shandong Province [2016GSF201100]
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center at the Sun Yat-sen University
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The study revealed a novel function of PDGF-D in activating complement pathways to promote macrophage polarization, and targeting the complement C3a receptor with SB290157 can alleviate PDGF-D-induced neuroinflammation and inhibit pathological choroidal neovascularization. Therapeutic strategies targeting both PDGF-D and the complement system may open up new possibilities for the treatment of neovascular diseases.
Platelet-derived growth factor-D (PDGF-D) is highly expressed in immune cells. However, the potential role of PDGF-D in immune system remains thus far unclear. Here, we reveal a novel function of PDGF-D in activating both classical and alternative complement pathways that markedly increase chemokine and cytokine responses to promote macrophage polarization. Pharmacological targeting of the complement C3a receptor using SB290157 alleviated PDGF-D-induced neuroinflammation by blocking macrophage polarization and inhibited pathological choroidal neovascularization. Our study thus suggests that therapeutic strategies targeting both PDGF-D and the complement system may open up new possibilities for the treatment of neovascular diseases.
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