title: Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration.
abstract: Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC, because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-β and PDGFR-α, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Chang
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People's Republic of China;
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Chunsik
authors.initials: C
authors.lastname: Lee
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Mingquan
authors.initials: M
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Lijuan
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Yida
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Medical Imaging Institute, Shandong Province Characteristic Key Subject, Medical Imaging and Nuclear Medicine, Binzhou Medical University, Yantai 264003, People's Republic of China;
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Weifang Medical University, Weifang 261053, People's Republic of China;
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Zijing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada R3E 3P5; and.
authors.forename: Hao
authors.initials: H
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Rong
authors.initials: R
authors.lastname: Ju
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China; lixr6@mail.sysu.edu.cn liuxl28@mail.sysu.edu.cn.
authors.forename: Xuri
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China; lixr6@mail.sysu.edu.cn liuxl28@mail.sysu.edu.cn.
authors.forename: Xialin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D010100:Oxygen; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D012162:Retinal Degeneration / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; C411423:platelet-derived growth factor C; D051547:Heme Oxygenase-1; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D010100:Oxygen
keywords: HMOX1; PDGF-CC; blood vessel regression; retinal degeneration; vasoprotective effect