Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration

被引：22

作者：

He, Chang ^{[1
]}

Zhao, Chen ^{[2
,3
]}

Kumar, Anil ^{[1
]}

Lee, Chunsik ^{[1
]}

Chen, Mingquan ^{[1
]}

Huang, Lijuan ^{[1
]}

Wang, Jing ^{[1
]}

Ren, Xiangrong ^{[1
]}

Jiang, Yida ^{[1
]}

Chen, Wei ^{[1
]}

Wang, Bin ^{[4
]}

Gao, Zhiqin ^{[5
]}

Zhong, Zheng ^{[1
]}

Huang, Zijing ^{[1
]}

Zhang, Fan ^{[1
]}

Huang, Bing ^{[1
]}

Ding, Hao ^{[6
]}

Ju, Rong ^{[1
]}

Tang, Zhongshu ^{[1
]}

Liu, Yizhi ^{[1
]}

Cao, Yihai ^{[7
]}

Li, Xuri ^{[1
]}

Liu, Xialin ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China

[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanjing 210029, Jiangsu, Peoples R China

[3] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China

[4] Binzhou Med Univ, Med Imaging Inst, Yantai 264003, Peoples R China

[5] Weifang Med Univ, Dept Cell Biol, Weifang 261053, Peoples R China

[6] Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB R3E 3P5, Canada

[7] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 41期

基金：

中国国家自然科学基金;

关键词：

PDGF-CC; vasoprotective effect; blood vessel regression; HMOX1; retinal degeneration; INHIBITS PATHOLOGICAL ANGIOGENESIS; GROWTH-FACTOR; MACULAR DEGENERATION; ALPHA-RECEPTOR; VEGF-B; SURVIVAL; FAMILY; PHOSPHORYLATION; EXPRESSION; APOPTOSIS;

D O I：

10.1073/pnas.1404140111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-beta and PDGFR-alpha, 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.

引用

页码：14806 / 14811

页数：6

共 25 条

[1] High level expression of angiopoietin-2 in human abscesses [J].

Bartus, Cynthia ;

Brown, Lawrence F. ;

Bonner, Michael Y. ;

Arbiser, Jack L. .

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2011, 64 (01) :200-201

[2] Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFR-αα and -αβ receptors [J].

Cao, RH ;

Bråkenhielm, E ;

Li, XR ;

Pietras, K ;

Widenfalk, J ;

Östman, A ;

Eriksson, U ;

Cao, YH .

FASEB JOURNAL, 2002, 16 (12) :1575-1583

[3] PDGF-C Mediates the Angiogenic and Tumorigenic Properties of Fibroblasts Associated with Tumors Refractory to Anti-VEGF Treatment [J].

Crawford, Yongping ;

Kasman, Ian ;

Yu, Lanlan ;

Zhong, Cuiling ;

Wu, Xiumin ;

Modrusan, Zora ;

Kaminker, Josh ;

Ferrara, Napoleone .

CANCER CELL, 2009, 15 (01) :21-34

[4] Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy [J].

Ferrara, Napoleone .

NATURE MEDICINE, 2010, 16 (10) :1107-1111

[5] Mechanisms of Cell Protection by Heme Oxygenase-1 [J].

Gozzelino, Raffaella ;

Jeney, Viktoria ;

Soares, Miguel P. .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2010, 50 :323-354

[6] Risk of Geographic Atrophy in the Comparison of Age-related Macular Degeneration Treatments Trials [J].

Grunwald, Juan E. ;

Daniel, Ebenezer ;

Huang, Jiayan ;

Ying, Gui-shuang ;

Maguire, Maureen G. ;

Toth, Cynthia A. ;

Jaffe, Glenn J. ;

Fine, Stuart L. ;

Blodi, Barbara ;

Klein, Michael L. ;

Martin, Alison A. ;

Hagstrom, Stephanie A. ;

Martin, Daniel F. .

OPHTHALMOLOGY, 2014, 121 (01) :150-161

[7] PDGF-CC blockade inhibits pathological angiogenesis by acting on multiple cellular and molecular targets [J].

Hou, Xu ;

Kumar, Anil ;

Lee, Chunsik ;

Wang, Bin ;

Arjunan, Pachiappan ;

Dong, Lijin ;

Maminishkis, Arvydas ;

Tang, Zhongshu ;

Li, Yang ;

Zhang, Fan ;

Zhang, Shi-Zhuang ;

Wardega, Piotr ;

Chakrabarty, Sagarika ;

Liu, Baoying ;

Wu, Zhijian ;

Colosi, Peter ;

Fariss, Robert N. ;

Lennartsson, Johan ;

Nussenblatt, Robert ;

Gutkind, J. Silvio ;

Cao, Yihai ;

Li, Xuri .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (27) :12216-12221

[8] Serious adverse events and visual outcomes of rescue therapy using adjunct bevacizumab to laser and surgery for retinopathy of prematurity. The Indian Twin Cities Retinopathy of Prematurity Screening database Report number 5 [J].

Jalali, Subhadra ;

Balakrishnan, Divya ;

Zeynalova, Zarifa ;

Padhi, Tapas Ranjan ;

Rani, Padmaja Kumari .

ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, 2013, 98 (04) :F327-F333

[9] A new member of an old family [J].

Kazlauskas, A .

NATURE CELL BIOLOGY, 2000, 2 (05) :E78-E79

[10] PDGF-C: a new performer in the neurovascular interplay [J].

Lee, Chunsik ;

Zhang, Fan ;

Tang, Zhongshu ;

Liu, Yizhi ;

Li, Xuri .

TRENDS IN MOLECULAR MEDICINE, 2013, 19 (08) :474-486

← 1 2 3 →