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The pathological retinal angiogenesis often causes blindness. Current anti-angiogenic therapy for proliferative retinopathy targets the vascular endothelial growth factor (VEGF), but many patients do not radically benefit from this therapy. Herein, we report that circulating prostaglandin (PG) F 2α metabolites were increased in type 2 diabetic patients with proliferative retinopathy, and the PGF 2α receptor (Ptgfr) was upregulated in retinal endothelial cells (ECs) from a mouse model of oxygen-induced retinopathy (OIR). Further, disruption of the PTGFR receptor in ECs attenuated OIR in mice. PGF 2α promoted the proliferation and tube formation of human retinal microvascular endothelial cells (HRMECs) via the release of ELR + CXC chemokines, such as CXCL8 and CXCL2. Mechanistically, the PGF 2α /PTGFR axis potentiated ELR + CXC chemokine expression in HRMECs through the G q /CAMK2G/p38/ELK-1/FOS pathway. Upregulated FOS-mediated ELR + CXC chemokine expression was observed in retinal ECs from PDR patients. Moreover, treatment with PTGFR inhibitor lessened the development of OIR in mice in a CXCR2-dependent manner. Therefore, inhibition of PTGFR may represent a new avenue for the treatment of retinal neovascularization, particularly in PDR.

Titel:	PGF <subscript>2α</subscript> facilitates pathological retinal angiogenesis by modulating endothelial FOS-driven ELR <superscript>+</superscript> CXC chemokine expression.
Autor/in / Beteiligte Person:	Zhao, Y ; Lei, Y ; Ning, H ; Zhang, Y ; Chen, G ; Wang, C ; Wan, Q ; Guo, S ; Liu, Q ; Xie, R ; Zhuo, Y ; Yan, S ; Zhao, J ; Wei, F ; Wang, L ; Wang, X ; Li, W ; Yan, H ; Yu, Y
Link:	Full Text Finder (Volltext)
Zeitschrift:	EMBO molecular medicine, Jg. 15 (2023-01-11), Heft 1, S. e16373
Veröffentlichung:	2024- : [London] : Nature Publishing Group ; <i>Original Publication</i>: Chichester, West Sussex : Wiley-Blackwell, 2023
Medientyp:	academicJournal
ISSN:	1757-4684 (electronic)
DOI:	10.15252/emmm.202216373
Schlagwort:	Humans Mice Animals Endothelial Cells metabolism Vascular Endothelial Growth Factor A metabolism Neovascularization, Pathologic pathology Oxygen Mice, Inbred C57BL Placenta Growth Factor Chemokines, CXC physiology Retinal Diseases pathology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [EMBO Mol Med] 2023 Jan 11; Vol. 15 (1), pp. e16373. <i>Date of Electronic Publication: </i>2022 Dec 13. MeSH Terms: Chemokines, CXC* / physiology ; Retinal Diseases* / pathology ; Humans ; Mice ; Animals ; Endothelial Cells / metabolism ; Vascular Endothelial Growth Factor A / metabolism ; Neovascularization, Pathologic / pathology ; Oxygen ; Mice, Inbred C57BL ; Placenta Growth Factor References: N Engl J Med. 2011 Feb 17;364(7):603-15. (PMID: 21323540) ; Am J Ophthalmol. 2011 Sep;152(3):406-412.e3. (PMID: 21723532) ; BMC Bioinformatics. 2011 Aug 04;12:323. (PMID: 21816040) ; J Biochem. 2015 Feb;157(2):73-80. (PMID: 25480981) ; Antioxidants (Basel). 2020 Jun 12;9(6):. (PMID: 32545552) ; J Biol Chem. 1999 Dec 10;274(50):35944-9. (PMID: 10585482) ; Science. 1995 Jul 21;269(5222):403-7. (PMID: 7618106) ; Ann Rheum Dis. 2011 Mar;70 Suppl 1:i109-12. 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PGF <subscript>2α</subscript> facilitates pathological retinal angiogenesis by modulating endothelial FOS-driven ELR <superscript>+</superscript> CXC chemokine expression.