Macrophage Sult2b1 promotes pathological neovascularization in age-related macular degeneration. 2023

Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Disordered immune responses and cholesterol metabolism have been implicated in age-related macular degeneration (AMD), the leading cause of blindness in elderly individuals. SULT2B1, the key enzyme of sterol sulfonation, plays important roles in inflammation and cholesterol metabolism. However, the role and underlying mechanism of SULT2B1 in AMD have not been investigated thus far. Here, we report that SULT2B1 is specifically expressed in macrophages in choroidal neovascularization lesions. Sutl2b1 deficiency significantly reduced leakage areas and inhibited pathological angiogenesis by inhibiting M2 macrophage activation in vivo and in vitro. Mechanistically, loss of Sult2b1 activated LXRs and subsequently increased ABCA1 and ABCG1 (ABCA1/G1)-mediated cholesterol efflux from M2 macrophages. LXR inhibition (GSK2033 treatment) in Sult2b1 macrophages reversed M2 polarization and decreased intracellular cholesterol capacity to promote pathological angiogenesis. In contrast to SULT2B1, STS, an enzyme of sterol desulfonation, protected against choroidal neovascularization development by activating LXR-ABCA1/G1 signalling to block M2 polarization. Collectively, these data reveal a cholesterol metabolism axis related to macrophage polarization in neovascular AMD.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013261 Sterols Steroids with a hydroxyl group at C-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. (IUPAC Steroid Nomenclature, 1987) Sterol
D014792 Visual Acuity Clarity or sharpness of OCULAR VISION or the ability of the eye to see fine details. Visual acuity depends on the functions of RETINA, neuronal transmission, and the interpretative ability of the brain. Normal visual acuity is expressed as 20/20 indicating that one can see at 20 feet what should normally be seen at that distance. Visual acuity can also be influenced by brightness, color, and contrast. Acuities, Visual,Acuity, Visual,Visual Acuities
D015238 Sulfotransferases Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2. Sulfotransferase
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular
D057135 Wet Macular Degeneration A form of RETINAL DEGENERATION in which abnormal CHOROIDAL NEOVASCULARIZATION occurs under the RETINA and MACULA LUTEA, causing bleeding and leaking of fluid. This leads to bulging and or lifting of the macula and the distortion or destruction of central vision. Degeneration, Wet Macular,Degenerations, Wet Macular,Macular Degeneration, Wet,Macular Degenerations, Wet,Wet Macular Degenerations
D020256 Choroidal Neovascularization A pathological process consisting of the formation of new blood vessels in the CHOROID. Neovascularization, Choroidal,Choroid Neovascularization,Neovascularization, Choroid,Choroid Neovascularizations,Choroidal Neovascularizations
D020533 Angiogenesis Inhibitors Agents and endogenous substances that antagonize or inhibit the development of new blood vessels. Angiogenesis Factor Inhibitor,Angiogenesis Inhibitor,Angiogenetic Antagonist,Angiogenetic Inhibitor,Angiogenic Antagonist,Angiogenic Antagonists,Angiogenic Inhibitor,Angiostatic Agent,Angiostatic Agents,Anti-Angiogenetic Agent,Anti-Angiogenic Drug,Anti-Angiogenic Drugs,Antiangiogenic Agent,Neovascularization Inhibitor,Neovascularization Inhibitors,Angiogenesis Factor Inhibitors,Angiogenetic Antagonists,Angiogenetic Inhibitors,Angiogenic Inhibitors,Antagonists, Angiogenic,Anti-Angiogenesis Effect,Anti-Angiogenesis Effects,Anti-Angiogenetic Agents,Antiangiogenesis Effect,Antiangiogenesis Effects,Antiangiogenic Agents,Inhibitors, Angiogenesis,Inhibitors, Angiogenetic,Inhibitors, Angiogenic,Inhibitors, Neovascularization,Agent, Angiostatic,Agent, Anti-Angiogenetic,Agent, Antiangiogenic,Agents, Angiostatic,Agents, Anti-Angiogenetic,Agents, Antiangiogenic,Antagonist, Angiogenetic,Antagonist, Angiogenic,Antagonists, Angiogenetic,Anti Angiogenesis Effect,Anti Angiogenesis Effects,Anti Angiogenetic Agent,Anti Angiogenetic Agents,Anti Angiogenic Drug,Anti Angiogenic Drugs,Drug, Anti-Angiogenic,Drugs, Anti-Angiogenic,Effect, Anti-Angiogenesis,Effect, Antiangiogenesis,Effects, Anti-Angiogenesis,Effects, Antiangiogenesis,Factor Inhibitor, Angiogenesis,Factor Inhibitors, Angiogenesis,Inhibitor, Angiogenesis,Inhibitor, Angiogenesis Factor,Inhibitor, Angiogenetic,Inhibitor, Angiogenic,Inhibitor, Neovascularization,Inhibitors, Angiogenesis Factor

Related Publications

Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
April 2018, JCI insight,
Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
June 1993, American journal of ophthalmology,
Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
April 1999, Ophthalmology,
Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
November 2019, Investigative ophthalmology & visual science,
Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
July 1993, Ophthalmology,
Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
December 1990, Ophthalmology,
Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
December 2014, Expert opinion on biological therapy,
Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
January 2008, Advances in experimental medicine and biology,
Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
September 2022, Annals of translational medicine,
Yafang Wang, and Yang Liu, and Yan Wang, and Yidong Wu, and Zhixuan Chen, and Feng Wang, and Xiaoling Wan, and Fenghua Wang, and Xiaodong Sun
November 2018, Ophthalmology. Retina,
Copied contents to your clipboard!