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: Chang He, Chen Zhao, Anil Kumar, Chunsik Lee, Mingquan Chen, Lijuan Huang, Jing Wang, Xiangrong Ren, Yida Jiang, Wei Chen, Bin Wang, Zhiqin Gao, Zheng Zhong, Zijing Huang, Fan Zhang, Bing Huang, Hao Ding, Rong Ju, Zhongshu Tang, Yizhi Liu, Yihai Cao, Xuri Li, Xialin Liu
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 41 Pg. 14806-11 (Oct 14 2014) ISSN: 1091-6490 [Electronic] United States
• PMID: 25267616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lymphokines
• Platelet-Derived Growth Factor
• platelet-derived growth factor C
• Heme Oxygenase-1
• Receptor, Platelet-Derived Growth Factor alpha
• Receptor, Platelet-Derived Growth Factor beta
• Oxygen

Topics

• Animals
• Cell Survival (drug effects)
• Disease Models, Animal
• Endothelial Cells (drug effects, pathology)
• Heme Oxygenase-1 (metabolism)
• Lymphokines (metabolism, pharmacology)
• Mice
• Myocytes, Smooth Muscle (drug effects, pathology)
• Oxygen
• Platelet-Derived Growth Factor (metabolism, pharmacology)
• Receptor, Platelet-Derived Growth Factor alpha (metabolism)
• Receptor, Platelet-Derived Growth Factor beta (metabolism)
• Retinal Degeneration (enzymology, pathology, prevention & control)
• Retinal Vessels (drug effects, enzymology, pathology)
• Up-Regulation (drug effects)